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Journal of Ethnopharmacology 141 (2012) 761–774

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm

Review

Rheum australe D. Don: A review of its botany, ethnobotany, phytochemistry and


pharmacology
Maan Bahadur Rokaya a,∗ , Zuzana Münzbergová a,b , Binu Timsina c , Krishna Ram Bhattarai d
a
Institute of Botany, Academy of Sciences of the Czech Republic, Zamek 1, CZ-252 43 Průhonice, Czech Republic
b
Department of Botany, Faculty of Science, Charles University, Praha, Czech Republic
c
Institute for Environmental Studies, Faculty of Science, Charles University, Benatska 2, 128 01 Prague, Czech Republic
d
Ministry of Forest and Soil Conservation, District Plant Resources Office, Dhangadi, Kailali, Nepal

a r t i c l e i n f o a b s t r a c t

Article history: Ethnopharmacological relevance: Rheum australe D. Don (Polygonaceae) has been commonly used in tra-
Received 28 November 2011 ditional medicine for a wide range of ailments related to the circulatory, digestive, endocrine, respiratory
Received in revised form 26 March 2012 and skeletal systems as well as to infectious diseases.
Accepted 27 March 2012
Aim of the review: To provide the up-to-date information that is available on the botany, traditional uses,
Available online 5 April 2012
phytochemistry, pharmacology and toxicology of Rheum australe. Additionally, to highlight the possible
uses of this species to treat different diseases and to provide a basis for future research.
Keywords:
Materials and methods: The present review covers the literature available from 1980 to 2011. The infor-
Rheum australe
Rheum emodi
mation was collected from scientific journals, books, theses and reports via a library and electronic search
Anticancer (Google Scholar, Web of Science and ScienceDirect).
Antidiabetic Results: Ethnomedical uses of Rheum australe have been recorded from China, India, Nepal and Pakistan
Antifungal for 57 different types of ailments. The phytochemical studies have shown the presence of many sec-
Anti-inflammatory ondary metabolites belonging to anthraquinones, stilbenes, anthrones, oxantrone ethers and esters,
Antimicrobial chromones, flavonoids, carbohydrate, lignans, phenols and sterols. Crude extracts and isolated com-
Antioxidant pounds from Rheum australe show a wide spectrum of pharmacological activities, such as antidiabetic,
Hepatoprotective
anti-inflammatory, antifungal, antimicrobial, antioxidant, anticancer, hepatoprotective and immune-
Immuno-enhancing
enhancing activities, as well as a usefulness for improving renal function.
Nephroprotective activity
Conclusion: Rheum australe has been widely used source of medicine for years without any adverse effects.
Many studies have provided evidence for various traditional uses. However, there is a need for additional
studies of the isolated compounds to validate the traditional uses in human models. The present review
on the botany, traditional uses, phytochemistry and toxicity has provided preliminary information for
further studies and commercial exploitations of the plant.
© 2012 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
1.1. Taxonomy and morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
1.2. Distribution and propagation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
1.3. Trade and conservation status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
2. Vernacular names and traditional uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 763
3. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 763
4. Pharmacological reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
4.1. Anticancer activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768

Abbreviations: AAS, atomic absorption spectroscopy; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CAMP, The Conservation
Management Assessment Plan; CCl4 , carbon tetrachloride; DPPH, 2,2-diphenyl-1-picrylhydrazyl; GPT, glutamate pyruvate transaminase; LDH, lactic dehydrogenase; LPI,
lipid peroxidation; MeOH, methanolic extract; MIC, minimal inhibitory concentration; NRs, Nepali Rupees; R. australe, Rheum australe; R. emodi, Rheum emodi; TBIL, total
bilirubin; W-INS, methanolic water-insoluble; W-S, methanolic water-soluble.
∗ Corresponding author.
E-mail address: rokayamaan@gmail.com (M.B. Rokaya).

0378-8741/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jep.2012.03.048
762 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

4.2. Antidiabetic activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768


4.3. Antifungal and antimicrobial activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
4.4. Anti-inflammatory activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
4.5. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
4.6. Hepatoprotective activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
4.7. Immuno-enhancing activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
4.8. Nephroprotective activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
5. Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773

1. Introduction is rhomboid-obovoid, and the stigma is oblate and muricate. The


fruit is ovoid-ellipsoid, broadly ellipsoid or ovoid-oblong in shape,
The use of medicinal plants in the Indian subcontinent can be large (0.5–1.5 cm), long and purple, with wings more narrow than
traced back to the Vedic period. The texts mentioning the uses thick and notched at both ends. Rheum australe flowers from June to
of different medicinal plants are the Rigveda (written between August and fruits from July to September (Li et al., 2003; see Fig. 1).
4500 and 1600 BC), the Atharveveda (2000–1000 BC), the Charaka
Samhita (∼900 BC) and the Sushruta Samhita (∼600 BC); these 1.2. Distribution and propagation
texts are written in Sanskrit (Anonymous, 1970; Singh et al., 1979;
Dev, 1999). Various ancient texts have mentioned Rheum australe D. Rheum australe is endemic to the Himalayan region, covering the
Don (Polygonaceae) being used for udara roga (stomach problems), areas of Bhutan, China (southern Tibet or S. Xizang), India (Kashmir,
amala pitta (gastritis), yakrit vikar (liver diseases), rakta moksha Sikkim), Myanmar, Nepal and Pakistan. It grows in grassy or rocky
(blood purification) and rakta pradhara (menstrual problems). In slopes at higher altitudes and in forest margins at an altitude of
addition to the Ayurveda system, Rheum australe is widely used 3200–5200 m (Press et al., 2000; Li et al., 2003).
in many traditional medical systems, such as the Chinese, home- Plant propagation is by either rootstocks or seeds. Rootstocks
opathic, Tibetan and Unani systems (Anonymous, 1972; Coburn, can be cut into pieces. They can successfully sprout when planted
1984; Lama et al., 2001; Babu et al., 2003; Bhatia et al., 2011; Rokaya in soil in Rheum australe’s natural habitat or in cultivated land dur-
et al., 2010). ing May through June. Mature seed collected at the end of October
There has been a tremendous interest in Rheum australe, as evi- will successfully germinate both when sown in Rheum australe’s
denced by the many studies carried out in recent years (e.g., Zargar natural habitat or in cultivated land at the beginning of November,
et al., 2011 and references there in). It is important to establish immediately after collection (Nautiyal et al., 2002), or in February
an association between the traditional uses and the recent studies through April (Bhattarai and Ghimire, 2006). Germination starts
of Rheum australe, as has been performed for many other plants after 7–10 days and continues for one month, and better germina-
(e.g., Singh et al., 2011; Patel et al., 2011). The present review com- tion occurs when the seeds are soaked in water for 10–12 h before
piles the fragmented information on the botany, traditional uses, sowing (Bhattarai and Ghimire, 2006). It is best to maintain the
phytochemistry, pharmacology and toxicology of this plant. We seedlings for one year in the same sown area and then to trans-
hope that this information will highlight the importance of Rheum plant them in March or April to another place. Propagation is best in
australe and will provide a new direction for researchers in the well-drained, sandy, porous soil that is rich in humus. Petioles can
future. Specifically, we aimed to answer the following questions. be harvested after a year, but good rootstocks with the highest per-
(1) What information is available on the traditional uses, botany, centage of active contents are obtained 4–5 years after germination
phytochemistry and toxicity of Rheum australe? (2) Are there any (Nautiyal et al., 2002).
pharmacological studies that validate its traditional uses? (3) What There have been attempts to develop in vitro techniques for the
are the different therapeutic potentials and future research oppor- mass propagation of Rheum australe from the shoot tip leaves (Lal
tunities for Rheum australe? and Ahuja, 1989, 1993), the rhizome buds or the stem segments
(Pandey et al., 2008; Malik et al., 2009). These techniques, how-
1.1. Taxonomy and morphology ever, remain experimental procedures, and additional studies are
required for improved output.
Rheum australe D. Don was first collected by N. Wallich between
1828 and 1849 (1727.1, lectotype of Rheum australe deposited in 1.3. Trade and conservation status
Kew) and was described by Don in Prodromus Florae Nepalensis
(1825). The synonym of Rheum emodi Wall. ex Meisn. given by C. Like most medicinal plants, Rheum australe is generally col-
Meissner in 1832 was a misnomer; thus, Rheum australe is used as lected from the wild (Edwards, 1996; Acharya and Rokaya,
the accepted name (Press et al., 2000). 2005; MoFSC/DF (2008/2009)). According to a report from Nepal
Rheum australe (2n = 22, 44) is a robust, perennial, 1–2 (-3) m (MoFSC/DF (2008/2009)), the total traded amount of Rheum australe
tall, glabrous herb with stout rhizomes. The stems are glabrous or in 2009 was 47,066 kg, with total revenue amounting to 467,895
pubescent at the nodes. The basal leaves have 30–40 long petioles Nepali Rupees (NRs) (6684 US$, 1 US$ = 70 NRs). As per Forest
and thick blades. The leaves are thick, orbicular, ovate-elliptic or regulations (1995), the revenue for rootstock is 5 NRs per kg and for
broadly ovate with 5–7 basal veins, a cordate base, entire margin petioles is 3 NRs per kg (MoFSC/FDP, 1995). The Conservation Man-
and sinuolate with an obtuse apex. The upper leaves are smaller. agement Assessment Plan (CAMP) workshop held in Nepal (2001)
The inflorescence is large, fastigiately branched and densely papil- classified Rheum australe as vulnerable due to the threat of over-
liferous. The flowers are pedicellate and dark purple. The perianth harvesting for trade. Moreover, this species falls under the list of
is spreading, 3–3.5 mm; the three outer parts of the perianth are 30 prioritised medicinal and aromatic plants that was developed by
smaller and oblong-elliptic. The filaments are subulate. The ovary the Government of Nepal and is highly recommended for research
M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 763

Fig. 1. Rheum australe (a) seedling; (b) mature plant; (c) unripe seeds; (d) cross-section of mature rootstocks.

and cultivation (MoFSC/DPR, 2006). In India, it is also classified 2002; Krenn et al., 2003; Babu et al., 2004; Krenn et al., 2004; Liu
as endangered due to commercial exploitation. For international et al., 2007).
trade, Rheum australe requires either a ‘certificate of cultivation’ or Studies of inorganic elements present in rootstocks of Rheum
a ‘legal procurement certificate’ from the designated forest author- australe by AAS have shown the presence of 19 elements from
ities (Nautiyal et al., 2002). wild/cultivated plants (Hameed et al., 2008; Singh et al., 2010;
Haq and Ullah, 2011). Table 4 shows the details of the secondary
2. Vernacular names and traditional uses

Rheum australe (Fig. 1) is commonly known as Himalayan


Table 1
rhubarb, or the red-veined pie plant in English and padamchal in
Vernacular names of Rheum australe.
the Nepali language (Manandhar, 2002). It is known by various
vernacular names in different geographical regions (see Table 1). Names Region/language/system
of medicine
Table 2 lists the ethnomedicinal uses of Rheum australe for 57
different types of ailments in China, India, Nepal and Pakistan. It is Aakchhyo, Atchowa, Chyurcha Sherpa
used to treat simple ailments (e.g., cough/cold, cuts) to very compli- Akase chuk, Padamchal, Chulthi amilo, Nepali
Shankhatra
cated ailments (e.g., malaria and kidney stones). It also has a wide
Akcyowa, Rheuchini Solukhumbu
range of veterinary uses, and sometimes, the plants are considered Amalaparni, Amlavetasa, Pitamulika Sanskrit
to be a general panacea for livestock (Coburn, 1984; see Table 3). Amlaparni, Pitamuuli, Gandhini Revatikaa. Ayurvedic
In addition to the medicinal uses, rhizomes that are soaked Revandachini
Archa, Archu Hindi
with water are used for herbal baths for babies to remove heat
Artho Bhote, Himachal and
from the body (Rokaya et al., 2010). The natural yellow dye Uttarakhand
obtained from the rhizomes is used in cosmetics, the colouring of Banglarevanchini Bengali
hair/textiles/wooden materials or as food colorant (Coburn, 1984; Chontal North Pakistan
Manandhar, 2002; Das et al., 2008; Malik et al., 2009; Rokaya et al., Chotial Swath valley, Pakistan
Chu tsa, Chu rtsa Amchi or Kham
2010). Sour-tasting petioles are used as spices, condiments, appe-
Chuchi, Chukri Hindi
tisers or digestants (Anonymous, 1982; Coburn, 1984; Kunwar and Chukedangla Jumla, Dolpa, Humla
Adhikari, 2005; Rokaya et al., 2010). In northern Pakistan, the leaves Chulthe, Dangle Chuk, Dool, Latte Chuk, Humli
are used as a vegetable (Shinwari and Gilani, 2003). Mire Chuk, Padamchaal, Padamchalnu,
Padamchalnya
Chulthi, Rebanda cini, Rebanxa cin, Revacini, Hindi
3. Phytochemistry Revandacini, Rubaba
Chungbar, Kyungpa rim Tamang
Rheum australe contains different secondary metabolites that Churtsa, Gyasa Tibetan
are categorised as anthraquinones (Fig. 2), stilbenes (Fig. 3), Chutial, Pumbachalan Kasmir
Dolu Bhote, Uttarakhand
anthrones, chromones, oxantrone ethers and esters, flavonoids Himalaya Daiou Japanese
(Fig. 4), carbohydrates, lignans, phenols and sterols. The frequently Indian Rhubarb, Himalayan Rhubarb, English
occurring active constituents of Rheum australe are anthraquinone Red-Veined Pie Plant
derivatives (aloe-emodin, chrysophanol, emodin, physcion and Khaghyo, Khaghyu, Puinju Gurung
Ladakirevanda chini, Raevaachini Marathi
rhein and their glycoside compounds) (Agarwal et al., 2000; Babu
Lichu Bhote, Himachal
et al., 2003; Singh et al., 2005a; Verma et al., 2005; Liu et al., Mire chuk Dolpali
2007; Malik et al., 2010a,b; Wang et al., 2010) and stilbene deriva- Mirechuk Danuwar
tives (piceatannol, resveratrol and their glycoside derivatives) (e.g., Naattu raevalchini Telugu
Agarwal et al., 2000; Krenn et al., 2003; Singh et al., 2005a; Padamchal Nepali
Revalchinikattai, Nattirevaichini, Siddha/Tamil
Verma et al., 2005; Ye et al., 2007; Malik et al., 2010a,b; Wang Nattumanjatchinnakkilangu
et al., 2010). Several complex compounds have also been isolated, Revandchini, Rewand Chini, Usara Rewand Unani
including torachrysone-8-O-␤-d-glucopyranoside, piceatannol-4 - Tarbu barter Kham
O-␤-d-(6 -O-p-coumaroyl)-glucopyranoside, sulphated emodin Tukshu Bhote, Himachal
Zang bian da huang Chinese
glucoside and acetylated chrysophanol glucoside (Pradhan et al.,
764 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

Table 2
Traditional uses of Rheum australe.

S.N. Ailment/use Plant part Mode of use Place/country Vernacular name Reference

1 Antidote Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Latif et al. (2006), Hamayun
et al. (2006a,b,c)
2 Antitoxin Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)
3 Antihelminthic Pet Chewed raw for treatment Dolpa, Humla, Jumla, Chulthi a, Chutsa, Late Kunwar et al. (2006), Ghimire
Mustang, Nepal chuk, Mirechuk, et al. (2001), Lama et al. (2001),
Padamchal, Tarbu battar Rokaya (2002)
milo
Rst Decoction or juice is used Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
Mirechuk, Padamchal, et al. (2001)
Tarbu battar
4 Appetizer Pet Eaten with common salt Jumla, Kalikot, Mugu, Nepal Akase chuk Bhattarai (1992), Kunwar and
raw or cooked Adhikari (2005), Kunwar et al.
(2006)
Rt Paste is used Nepal Padamchal, akashe chuk, DPR (1997, 2007), Joshi (2000),
Chulthi amilno Joshi and Joshi (2001), Baral
and Kurmi (2006)

5 Asthma Pet Extracts from petioles are Syangja, Parbat, Kaski; Khaghyo, Khaghyu Shrestha and Dhillion (2003)
applied on forehead Nepal
Rh Powder roasted with Nanda Devi, India Archu, Chukri, Leechu Rana et al. (2010)
butter, made into pills and
one pill is taken twice a
day for 30–45 days
Rh, Lvs Unspecified India; Valley Swat, Pakistan Chukri, Leechu; Chotial Jain (1991), Hamayun et al.
(2006a,b,c)

6 Back pain Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c)
7 Bile disorder/Bile Rst Rootstocks are pounded, Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
fever mixed with other herbs Mirechuk, Padamchal, et al. (2001), Rokaya et al.
and consumed Tarbu battar (2010)
Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c)

8 Bleeding (internal Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)
or external)
9 Bloated stomach Rst Rootstocks are pounded, Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
mixed with other herbs Mirechuk, Padamchal, et al. (2001)
and consumed Tarbu battar
10 Blood Rst Decoction or tea is drunk Manang and Walangchung Padamchal Shrestha et al. (1995), Sherpa
disorder/blood Gola, Kanchunjunga area, (2001), Ghimire and Nepal
purification Nepal (2007)
Rst Rootstocks are pounded, Dolpa, Humla, Nepal Amilo, Chuk, Chulthe, Ghimire et al. (2001), Lama
mixed with other herbs or Chulthi amilo, Chutsa, et al. (2001), Rokaya et al.
consumed singly Mirechuk, Padamchal, (2010)
Tarbu battar
Rst Unspecified Bulashbar nullah, Pakistan; Chukri, Leechu; Chontal, Shinwari and Gilani (2003),
Swat valley, Pakistan Chotial Hamayun et al. (2006a,b,c),
Latif et al. (2006)
Pet Extracts from petioles are Syangja, Parbat, Kaski; Khaghyo, Khaghyu Coburn (1984)
applied on forehead Nepal
11 Body ache/Body Rt Paste is applied on affected Dolakha, Syangja, Parbat, Chu tsa, Khaghyo, Coburn (1984), Acharya and
pain/Muscular pain part Kaski and Kathmandu, Khaghyu, Padamchal Rokaya (2005)
Nepal
Rt, Pet, Lvs Decoction or tea is drunk Walangchung Gola, Padamchal Sherpa (2001), Ghimire and
Kanchunjunga area, Nepal Nepal (2007)
Rh Paste and turmeric powder Ukhimanth, Uttarakhand, Archu Semwal et al. (2010)
mixed with refined fat is India
applied
12 Body cramp Rt Powder is taken with water Rasuwa, Nepal Puinju, Padamchal Joshi and Edington (1990),
Manandhar (2002), DPR (2007)
Rh Unspecified Jaunsar region, Dehradun, Archa, Archu, Chuchi, Rastogi and Mehrotra (1998),
Uttarakhand, India; Swat Chukri, Dolu, Leechu; Chauhan (1999), Bhatt and
valley, Pakistan Chotial, Tukshu Negi (2006), Hamayun et al.
(2006a,b,c), Latif et al. (2006),
Bisht and Badoni (2009)

13 Boils Rh Decoction mixed with ghee Lahul-Spiti, Himachal, Tukshu, Lichu, Artho, Lal and Singh (2008)
or oil is applied twice a day India Chucha
for 2–3 days around boils
14 Bone ache Rh Paste is fried with turmeric Jaunsar region, Dehradun, Archu, Dolu Bhatt and Negi (2006)
and ghee and applied India
15 Fractured or Rst Paste is applied on Dolakha, Dolpa, Humla, Chu tsa, Khaghyo, Coburn (1984), Pohle (1990),
broken fractured or broken bones, Jumla, Kask, Manang, Khaghyu, Late chuk, Mire Rokaya (2002), Shrestha and
bones/sprains or sprained body part Mustang, Parbat, Syangja, chuk, Padamchal Dhillion (2003), Kunwar and
Nepal Adhikari (2005), Kunwar et al.
(2006)
M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 765

Table 2 (Continued)

S.N. Ailment/use Plant part Mode of use Place/country Vernacular name Reference

Rst Rootstocks are pounded, Dolpa, Manang, Nepal Chulthi amilo, Chutsa, Shrestha et al. (1995), Ghimire
mixed with other herbs, Mirechuk, Padamchal, et al. (2001), Lama et al. (2001)
consumed and applied Tarbu battar
externally
Rst About 50 g powder is Makalu-Barun, Nepal Chhyoma, Churcha, Chaudhary et al. (2002)
mixed with about 200 g of Padamchal
paste of Viscum articulatum
and applied once around
fractured part of the body
by the Sherpa community
in Seduwa sector
Pet, Lvs Unspecified Walangchung Gola, Padamchal Sherpa (2001), Ghimire and
Kanchunjunga area, Nepal Nepal (2007)

16 Bronchitis Rh Powder roasted with Nanda Devi, India Archu, Chukri, Leechu Rana et al. (2010)
butter, made into pills and
one pill is taken twice a
day for 30–45 days
Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c)

17 Bruises Rh Unspecified Jaunsar region, Dehradun, Archu, Dolu Bhatt and Negi (2006)
India
Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c)

18 Burns Rt Paste is applied on affected Kathmandu, Nepal Padamchal Acharya and Rokaya (2005)
part
19 Chest pain Rst Consumed with water Dolpa, Humla, Jumla, Late chuk, mire chuk, Kunwar et al. (2006)
Mustang, Nepal padamchal
20 Cold Rst Consumed with water Dolpa, Humla, Jumla, Late chuk, mire chuk, Kunwar et al. (2006)
Mustang, Nepal padamchal
Pet, Rts Roots are crushed, boiled Humla, Nepal Amilo, Chuk, Chulthe, Rokaya et al. (2010)
and consumed Padamchal
Rh Paste is taken orally Ukhimanth, Uttarakhand, Archu Semwal et al. (2010)
India
21 Constipation Pet, Rts Roots are crushed, boiled Humla, Nepal Amilo, Chuk, Chulthe, Rokaya et al. (2010)
and consumed Padamchal
Wh pl Powder is administered Swat Kohistan, Pakistan Chotial Hamayun et al. (2006b)
with water
Rst One tea spoon powder with Manaslu, Nepal Padamchal Pyakurel and Gurung (2006)
lukewarm water is taken
once a day in bed time
Rt Paste is used taken with Nepal Padamchal, akashe chuk, DPR (1997), Joshi (2000), Joshi
water Chulthi amilno and Joshi (2001), Rokaya
(2002), Baral and Kurmi (2006)
Rh The watery extract is given Parvati valley, India Chukri, Leechu Sharma et al. (2004)
orally
22 Cough Rst Consumed with water Dolpa, Humla, Jumla, Late chuk, mire chuk, Kunwar et al. (2006)
Mustang, Nepal padamchal
Pet, Rts Roots are crushed, boiled Humla, Nepal Amilo, Chuk, Chulthe, Rokaya et al. (2010)
and consumed Padamchal
Rh Paste is taken orally Ukhimanth, Uttarakhand, Archu Semwal et al. (2010)
India
Rh Unspecified India Chukri, Leechu Jain (1991)
Lvs Unspecified Bulashbar nullah, Pakistan Chukri, Leechu; Chontal Shinwari and Gilani (2003)
Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)

23 Cuts Rst Decoction is externally Manang, Nepal Padamchal Shrestha et al. (1995)
applied
Rts Paste is applied externally Garwal, Nanda Devi; Chukri, Leechu, Padamchal Aswal (1996), Nautiyal et al.
Kishtwar, Jammu and (2003), Sharma et al. (2004),
Kashmir; Parvati valley, Acharya and Rokaya (2005),
India; Kathmandu, Nepal Kumar et al. (2009)
Pet, Lvs Unspecified Walangchung Gola, Archa, Chuchi, Chukri, Chauhan (1999), Sherpa
Kanchunjunga area, Nepal; Tukshu, Padamchal (2001), Ghimire and Nepal
Himachal India (2007)

24 Diarrhoea Pet, Rts Roots are crushed, boiled Humla, Nepal Amilo, Chuk, Chulthe, Rokaya et al. (2010)
and consumed Padamchal
Rst Juice is consumed Dolpa, Humla, Jumla, Chhurcha, Late chuk, mire Kunwar et al. (2006), Uprety
Mustang, Rasuwa, Nepal chuk, Padamchal et al. (2010)
Rst Powder/paste is consumed Syabru, Nepal Padamchal, akashe chuk, Joshi and Edington (1990), DPR
orally Chulthi amilno (1997), Joshi (2000), Joshi and
Joshi (2001), Baral and Kurmi
(2006)

25 Digestive Pet Eaten fresh or dried in raw Dolakha, Syangja, Parbat, Chu tsa, Khaghyo, Coburn (1984)
or cooked form Kaski; Nepal Khaghyu, Padamchal
766 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

Table 2 (Continued)

S.N. Ailment/use Plant part Mode of use Place/country Vernacular name Reference

26 Diuretic Pet Decoction or juice is used Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
Mirechuk, Padamchal, et al. (2001)
Tarbu battar
Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c),
Latif et al. (2006)

27 Dysentery Rt Powder/paste is taken with Tamil Nadu, India; Dolpa, Latechuk, Padamchal Kunwar and Adhikari (2005);
water Humla, Jumla, Mustang, Kunwar et al. (2006), DPR
Nepal (2007), Dixit (2011)
Rh The watery extract is given Parvati valley, Ukhimanth, Archu, Chukri, Leechu Sharma et al. (2004), Semwal
orally Uttarakhand, India et al. (2010)

28 Earache Rh The rhizome juice is Parvati valley, India Chukri, Leechu Sharma et al. (2004)
dropped in eaching ear
29 Eye problems/sore Rh, Lvs Unspecified Valley Swat, Pakistan Chotial Hamayun et al. (2006a,b,c)
eyes
30 Fever Rst Juice is consumed Rasuwa, Nepal Chhurcha, Padamchaal Uprety et al. (2010)
Rt Paste is applied on head or Dolakha, Syangja, Parbat, Chu tsa, Khaghyo, Coburn (1984)
body. Kaski; Nepal Khaghyu, Padamchal
Rh, Lvs Unspecified India and Valley Swat, Chotial, Chukri, Leechu, Jain (1991), Rokaya (2002),
Pakistan and Dho-Tarap, Chu tsa Hamayun et al. (2006a,b,c)
Dolpa, Nepal
31 Flatulence Wh pl Unspecified Himachal, India Archo Sharma et al. (2011)
32 Frost bite Rh Paste is applied on affected Kashmir, India Pan Tsalen Malik et al. (2011)
body parts
33 Gastritis Pet/Rts Chewed raw or taken with Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
water Mirechuk, Padamchal, et al. (2001), Rokaya et al.
Tarbu battar (2010)
34 Goiter Rh 1 g of paste is given once a Niti valley, Uttarakhand, Dolu Phondani et al. (2010)
day for seven days India
35 Headache Rt Paste is applied to on the Dolakha, Syangja, Parbat, Chu tsa, latechuk, Khaghyo, Coburn (1984), Joshi and Joshi
forehead for relief Kaski Dolpa, Nepal and Khaghyu, Padamchal; (2001), Sharma et al. (2004),
Parvati valley, India Chukri, Leechu Kunwar and Adhikari (2005)
Pet, Rts Roots are crushed, boiled Humla, Nepal Aakashe chuk, Amilo, Chuk, DPR (1997), Joshi (2000), Joshi
and consumed Chulthe, Padamchal and Joshi (2001), Rokaya
(2002), Baral and Kurmi (2006)

36 Hematochezia Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)


37 Heat repellent Rts Rhizomes soaked water is Humla, Nepal Amilo, Chuk, Chulthe, Rokaya et al. (2010)
used for bathing babies and Padamchal
this action is believed to
throw away excessive heat
from the body
Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)

38 Indigestion Rst Juice/powder or infusion Dolpa, Humla, Kathmandu, Amilo, Chhurcha, Chuk, DPR (1997), Joshi (2000),
after crushing and boiling Rasuwa, Nepal. Chulthe, Chulthi amilo, Ghimire et al. (2001), Joshi and
is consumed alone or Chutsa, Mirechuk, Joshi (2001), Lama et al. (2001),
mixed with herbs Padamchaal, Padamchal, Rokaya (2002), Acharya and
Tarbu battar Rokaya (2005), Baral and
Kurmi (2006), Rokaya et al.
(2010), Uprety et al. (2010)
Lvs Unspecified Bulashbar nullah, Pakistan Shinwari and Gilani (2003)

39 Injury (internal) Rst Decoction or tea is drunk Walangchung Gola, Padamchal Sherpa (2001), Ghimire and
Kanchunjunga area, Nepal Nepal (2007)
Rh Paste is taken orally Ukhimanth, Uttarakhand, Archu Semwal et al. (2010)
India
40 Injury (external) Rh Paste is mixed with water Parvati valley, India Chukri, Leechu Sharma et al. (2004)
and applied externally
Rt Paste is taken orally with Nepal Padamchal Joshi and Joshi (2001)
turmeric
41 Joint pain Rts Powder mixed with Kishtwar, Jammu and Chukri Kumar et al. (2009)
mustard oil is applied on Kashmir, India
joints
42 Kidney Rh The powder is mixed with Swat Kohistan, Pakistan Chotial Hamayun et al. (2006a,b,c)
stone/kidney egg, fried in desi ghee and
problems used twice a day
43 Laxative Rt Paste is used Nepal Padamchal, akashe chuk, DPR (1997, 2007), Joshi (2000),
Chulthi amilno Baral and Kurmi (2006)
Rt About 2 g paste and eaten Jumla, Nepal Akase chuk, Chulthi amilo Manandhar (1980, 1986),
with warm milk or with Bhattarai (1992)
water
Rh, Lvs Unspecified Bulashbar nullah, Swat Archa, Chuchi, Chukri, Rastogi and Mehrotra (1998),
valley, Pakistan and Chontal, Chotial, Chukri, Chauhan (1999), Shinwari and
Uttarakhand, Himachal, Leechu, Tukshu Gilani (2003), Hamayun et al.
India (2006a,b,c), Latif et al. (2006),
Bisht and Badoni (2009)
M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 767

Table 2 (Continued)

S.N. Ailment/use Plant part Mode of use Place/country Vernacular name Reference

44 Malarial fever Rh Powder is consumed orally Mustang, Nepal Padamchal Bhattarai et al. (2010)
once a day with milk or hot
water until cure
45 Menstrual disorder Rst Rootstocks are pounded, Dolpa, Humla, Nepal Amilo, Chuk, Chulthe, Ghimire et al. (2001), Lama
mixed with other herbs or Chulthi amilo, Chutsa, et al. (2001), Rokaya (2002),
alone and consumed Mirechuk, Padamchal, Rokaya et al. (2010)
Tarbu battar
Rh, Lvs Unspecified Valley Swat, Pakistan Chotial, Chukri Hamayun et al. (2006a,b,c),
Latif et al. (2006)

46 Mumps Rh Paste is mixed with water Parvati valley, India Chukri, Leechu Sharma et al. (2004)
and applied externally
Rts Unspecified Himachal, Kishtwar, Archa, Chuchi, Chukri, Chauhan (1999), Kumar et al.
Jammu and Kashmir, India Tukshu (2009)

47 Piles Rh, Lvs Unspecified Valley Swat, Pakistan and Chotial, Chukri, Leechu Jain (1991), Hamayun et al.
India (2006a,b,c)
48 Rheumatism Rh Paste is applied for Helambu, Jumla, Kalikot, Akase chuk, Aakchhyo, Bhattarai (1989), Kunwar et al.
massaging on the affected Mugu, Nepal Atvhowa, Chyurcha (2006)
part
49 Scabies/Skin Rst Paste is applied on skin Makalu-Barun, Nepal Chhyoma, Churcha, Chaudhary et al. (2002)
disease or eruption every Tuesday for 3 weeks Padamchal
by the Rai community in
Tamku area, Nepal
Rt Paste is used Nepal Padamchal, akashe chuk, DPR (1997), Joshi (2000), Joshi
Chulthi amilno and Joshi (2001), Baral and
Kurmi (2006)
Rt Decoction is applied twice Lahul-Spiti, Himachal, Tukshu, Lichu, Artho, Lal and Singh (2008)
a day for 2–3 days India Chucha
Rh Unspecified India Chukri, Leechu Jain (1991)

50 Sore-throat Rst Decoction is drunk Manang, Nepal Padamchal Shrestha et al. (1995)
51 Stomach ache Rst Juice is consumed Rasuwa, Nepal Chhurcha, Padamchaal Uprety et al. (2010)
Rh The watery extract is given Parvati valley, India Chukri, Leechu Sharma et al. (2004)
orally
Rh Powder roasted with Nanda Devi, India Archu, Chukri, Leechu Rana et al. (2010)
butter, made into pills and
one pill is taken twice a
day for 30–45 days
Lvs Unspecified Bulashbar nullah, Swat Akase chuk, Chontal, Manandhar (2002), Shinwari
valley, Pakistan; Kishtwar, Chotial, Chukri, Chulthi and Gilani (2003), Hamayun
Jammu and Kashmir, India; amilo, Leechu, Padamchal et al. (2006a,b,c), Kumar et al.
Nepal (2009)
Rh Paste is taken orally Ukhimanth, Uttarakhand, Archu Semwal et al. (2010)
India
Rh/Rt Unspecified Himachal, India Archa, Chuchi, Chukri, Chauhan (1999)
Tukshu
52 Swelling Rst Rootstocks are grinded, Dolpa, Nepal Chulthi amilo, Chutsa, Ghimire et al. (2001), Lama
mixed with other herbs Mirechuk, Padamchal, et al. (2001), Rokaya (2002)
and consumed Tarbu battar
Rh Whole plant is crushed and Chhota Bhangal, Himachal, Chukri Uniyal et al. (2006)
poultice is made in a cotton India
cloth. This is then heated
and applied affected part
Rts Unspecified Himachal, Kishtwar, Chukri Chauhan (1999), Kumar et al.
Jammu and Kashmir, India (2009)

53 Teeth cleaning Rt Powder is used in teeth Kathmandu, Nepal and Archa, Chuchi, Chukri, Chauhan (1999), Acharya and
cleaning Himachal, India Tukshu, Padamchal Rokaya (2005)
54 Tonic Rh Paste is used Himachal, India; Nepal Chulthi amilo, Chukri, Manandhar (1980, 2002),
Leechu; Akase chuk, Rastogi and Mehrotra (1998),
Padamchal DPR (1997, 2007), Chauhan
(1999), Joshi (2000), Joshi and
Joshi (2001), Baral and Kurmi
(2006)
55 Tonsilitis/swelling Rh The watery extract is given Parvati valley, India Chukri, Leechu Sharma et al. (2004)
of the throat orally
Rts Unspecified Himachal, Kishtwar, Archa, Chuchi, Chukri, Chauhan (1999), Kumar et al.
Jammu and Kashmir, India Tukshu (2009)
Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)

56 Ulcer Rt Powder is applied Nepal Padamchal, akashe chuk, DPR (1997), Joshi (2000), Joshi
Chulthi amilno and Joshi (2001), Baral and
Kurmi (2006)
Rh Unspecified India Chukri, Leechu Jain (1991)
768 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

Table 2 (Continued)

S.N. Ailment/use Plant part Mode of use Place/country Vernacular name Reference

57 Wounds Rh/Rt Powder is sprinkled over Himachal, India Archa, Chuchi, Chukri, Chauhan (1999)
the wound Chukri, Leechu, Tukshu
Rh Paste is applied on affected Garwal, Nanda Devi, Pan Tsalen Jain (1991), Aswal (1996),
body parts Kashmir, Parvati valley, Nautiyal et al. (2003), Sharma
Kishtwar, Jammu and et al. (2004), Malik et al.
Kashmir, India (2011), Kumar et al. (2009)
Rh Decoction mixed with ghee Lahul-Spiti, Himachal, Tukshu, Lichu, Artho, Lal and Singh (2008)
or oil is applied twice a day India Chucha
for 2–3 days
Rt Paste is used Dolpa, Nepal Chulthi amilo, Chutsa, DPR (1997), Joshi (2000),
Mirechuk, Padamchal, Ghimire et al. (2001), Joshi and
Tarbu battar Joshi (2001), Lama et al. (2001),
Rokaya (2002), Baral and
Kurmi (2006)
Rt Unspecified China Zang bian da huang Zhou et al. (2011a,b)

Note: Lvs, Leaves; Pet, Petiole; Rh, Rhizome; Rt, Root; Rst, Rootstock.

metabolites and inorganic elements present in the rootstocks of by reducing the neoplastic growth and malignancy that are often
Rheum australe. caused by oxidative stress (Zargar et al., 2011).

4. Pharmacological reports 4.2. Antidiabetic activities

4.1. Anticancer activity ␣-Glucosidase, which is associated with the sucrase–isomaltase


complexes of the mammalian intestine, is involved in the
Rajkumar et al. (2011a) tested the methanolic and aqueous digestion of carbohydrates and thus increases blood glucose
extracts of the Rheum australe rhizome in human breast car- levels. Babu et al. (2004) tested the effects of Rheum australe-
cinoma (MDA-MB-435S) and liver carcinoma (Hep3B) cell lines derived crude extracts and isolated compounds (rhapontigenin,
for cytotoxicity. They found that the extracts exhibited exten- desoxyrhaponticin, desoxyrhapontigenin, chrysophanol-8-O-␤-
sive concentration-dependent cytotoxicity in tested cells. Different d-glucopyranoside and torachrysone-8-O-␤-d-glucopyranoside)
studies of apoptosis induction by methanolic and aqueous extracts against yeast ␣-glucosidase and mammalian ␣-glucosidase.
of the Rheum australe rhizome in MDA-MB-435S (human breast Rhapontigenin was the most effective at inhibiting ␣-glucosidase,
carcinoma), Hep3B (human hepatocellular carcinoma) and PC-3 whereas the crude extract was the least effective. The great-
(human prostate cancer) cell lines have shown that the extracts est inhibition of mammalian ␣-glucosidase was caused by
cause apoptosis of the targeted cancerous cells, even at the low chrysophanol-8-O-␤-d-glucopyranoside, and the least inhibition
doses of 12.5–50 ␮g/ml (Rajkumar et al., 2011b). These results have was caused by the crude extract. However, rhapontigenin was
demonstrated a possible use of Rheum australe against tumours only fourth best at inhibiting mammalian ␣-glucosidase. Thus, the

Table 3
Veterinary uses of Rheum australe.

S.N. Ailment/use Plant part Mode of use Place/country Reference

1 Fractured or broken Rt Paste of Rheum australe is mixed Almora, Uttaranchal, India Pande et al. (2007), Shah et al.
bones with plaster of Chamarhmau (2008)
(Carpinus viminea) bark plastered
around bone and bandaged using
splints of Debregeasia salicifolia in
cattle
Rt paste is applied on the injured or Humla, Nepal Rokaya et al. (2010)
broken limbs for cattle.
2 Broken horn Rh Unspecified Uttaranchal, India Pande et al. (2007)
3 Constipation/purgative Rt Powder is mixed with wheat flour, Chotial, Pakistan Hamayun et al. (2006b)
boiled and given to cows, sheep,
donkeys, and goats.
4 Cuts Rh Unspecified Uttaranchal, India Pande et al. (2007)
5 Dysentery Paste is given orally. Darma valley, Pithoragarh, Uttaranchal, Tiwari and Pande (2006),
India Pande et al. (2007)
6 Eye diseases Rh Unspecified Uttaranchal, India Pande et al. (2007)
7 Haemachuria Rh Unspecified Uttaranchal, India Pande et al. (2007)
8 Hoof diseases Rh Unspecified Uttaranchal, India Pande et al. (2007)
9 Indigestion Rt Paste is given orally. Darma valley, Pithoragarh, Uttaranchal, Tiwari and Pande (2006),
India Pande et al. (2007)
10 Injury (internal/external) Rh Unspecified Uttaranchal, India Pande et al. (2007)
11 Mammary gland swelling Rh Unspecified Uttaranchal, India Pande et al. (2007)
(Mastitis)
12 Panacea Root Boiled roots are given to livestocks Syangja, Parbat, Kaski; Nepal Coburn (1984)
as general panacea
13 Skin diseases Rh Unspecified Uttaranchal, India Pande et al. (2007)
14 Wounds Rh Unspecified Uttaranchal, India Pande et al. (2007)

Note: Rh, Rhizome; Rt, Root; Rst, Rootstock.


M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 769

OH O OH OH O OH

OH
CH3
O O

1. Aloe-emodin 2. Chrysophanol

OH O OH OH O OH

OH
CH3 H3C
HO
O O
3. Emodin 4. Physcion

OH O OH O

H3 C O
O O O O OH
O OH
OH
OH
OH CH3
O
5. Rhein 6. 8-O-β-D-(6’-O-acetyl) glucopyranosyl-chrysophanol

O O O
O
CH3 HO O
O
HO O OH O O OH

C O OH OH
HO O OH HO CH3
OO
OH O
OH

OH H
OH
7. Chrysophanol 8-O-(6´-O-galloyl)-glucoside 8. Emodin 8-O-(6´-O-malonyl)-glucoside

OH

O
HO
HO O O O
OH
H

H3C
O
6. Torachrysone-8-O-β-D-glucopyranoside
Fig. 2. Some structures of anthraquinones isolated from rootstocks of Rheum australe.

Rheum australe rhizome could be useful for lowering glucose levels of the Rheum australe rhizome (250 mg/kg body weight) possess
after meals by slowing down the digestion of carbohydrates. antidiabetic properties because the extracts enhance the peripheral
Analyses of different enzymes (hexokinase, phosphoglu- utilisation of glucose (Radhika et al., 2010). In a separate experi-
coisomerase, aldolase, glucose-6-phosphatase and fructose-1, ment, 95% ethanol extracts and the compound stilbene glycoside
6-bisphosphatase) in alloxan monohydrate-induced (150 mg/kg, E obtained from Rheum australe rhizomes have been found to be
i.p.) diabetic albino rats have shown that the ethanol extracts hypoglycaemic (Li et al., 1997).
770 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

OH OH

HO
HO

HO
OH

OH

1. Piceatannol 2. Resveratrol

HO OH HO O
O C O OH
O
HO
OO
OH OH OH
HO
HO OH
HO OH H
OH
OH
OH
3. Piceatannol-3'-O-β-D-glucopyranoside 4 .Piceatannol-4′-O-β-D-(6″-O-galloyl)-glucopyranoside

OH
C OCH2 OH
O OO
OH
HO HO
OH OH

5. Piceatannol-4′-O-β-D-(6″-O-p-coumaroyl)-glucopyranoside
Fig. 3. Structures of some stilbenes isolated from rootstocks of Rheum australe.

4.3. Antifungal and antimicrobial activities were found to be more active than MeOH extracts, with an MIC
of 25–50 ␮g/ml. Sporotrichum schenckii was not sensitive to any
Studies have been performed on the effects of methanolic anthraquinone derivatives, and Aspergillus fumigatus was sensi-
(MeOH) crude extracts and Rheum australe-isolated anthraquinone tive only to chrysophanol at an MIC of 50 ␮g/ml (Agarwal et al.,
derivatives (rhein, physcion, aloe-emodin and chrysophanol) on 2000). In a different experiment, three compounds isolated from
the growth of different fungi (Candida albicans, Cryptococcus neo- the Rheum australe rhizome (revandchinone-1, 3 and 4) exhibited
formans, Sporotrichum schenckii, Trichophyton mentagrophytes and antifungal activity against Aspergillus niger and Rhizopus oryzae,
Aspergillus fumigatus) responsible for skin diseases in India. The with inhibition zone diameters of 8–9 and 9–11 mm for the 100 and
crude MeOH extracts exhibited a minimal inhibitory concentra- 150 ␮g/ml test concentrations, respectively. In the same experi-
tion (MIC ␮g/ml) of 250 ␮g/ml, except on Cryptococcus neoformans ment, the same three compounds were tested against gram positive
and Sporotrichum schenckii. The pure anthraquinone derivatives (Bacillus subtilis, Bacillus sphaericus and Staphylococcus aureus) and

OH HO O OH

HO
O
OH
O OH
O
R
OH

OH

42. Epicatechin
R
43. Carpusin or marsupsin CH3
44. Maesopsin H

Fig. 4. Structures of some flavonoids isolated from rootstocks of Rheum australe.


M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 771

Table 4
Summary of the secondary compounds and inorganic elements present in Rheum australe.

S.N. Class Compounds References

1 Anthraquinones 6-Methyl-aloe-emodin Singh et al. (2005b)


2 6-Methyl-aloe-emodin-triacetate Singh et al. (2005b)
3 6-Methylrhein Singh et al. (2005b)
4 6-Methyl-rhein-diacetate Singh et al. (2005b)
5 8-O-␤-d-(6 -O-acetyl) glucopyranosyl-chrysophanol Krenn et al. (2004)
6 Aloe-emodin Agarwal et al. (2000), Wang et al. (2010)
7 Chrysophanol Agarwal et al. (2000), Singh et al. (2005a), Babu et al. (2003, 2004),
Verma et al. (2005), Malik et al. (2010a,b), Wang et al. (2010)
8 Chrysophanol 1-O-glucoside Ye et al. (2007)
9 Chrysophanol 8-O-(6 -O-galloyl)-glucoside Ye et al. (2007)
10 Chrysophanol-8-O-␤-d-glucopyranoside Babu et al. (2004), Singh et al. (2005a), Malik et al. (2010a,b), Liu
et al. (2007), Wang et al. (2010), Verma et al. (2005)
11 Emodin Verma et al. (2005), Singh et al. (2005a), Malik et al. (2010a,b),
Wang et al. (2010), Liu et al. (2007), Babu et al. (2004)
12 Emodin 8-O-(2 , 3 , 4 , 6 -tetraacetyl)-glucoside Krenn et al. (2003)
13 Emodin 8-O-(6 -O-malonyl)-glucoside Ye et al. (2007)
14 Emodin 8-O-␤-d-glucopyranosyl-6-O-sulfate Krenn et al. (2003)
15 Emodin-8-O-␤-d-glucopyranoside Liu et al. (2007), Wang et al. (2010), Verma et al. (2005), Singh et al.
(2005a), Ye et al. (2007), Malik et al. (2010a,b)
16 Emodin-O-␤-d-glucoside Ye et al. (2007)
17 Physcion Agarwal et al. (2000), Verma et al. (2005), Singh et al. (2005a),
Babu et al. (2003), Malik et al. (2010a,b), Liu et al. (2007), Wang
et al. (2010), Babu et al. (2004)
18 Physcion-1-O-␤-d-glucopyranoside Wang et al. (2010)
19 Physcion-8-O-␤-d-glucopyranoside Wang et al. (2010)
20 Rhein Agarwal et al. (2000)
31 Torachrysone-8-O-␤-d-glucopyranoside Babu et al. (2004), Krenn et al. (2003)
22 Stilbenes Desoxyrhaponticin Babu et al. (2004)
23 Desoxyrhapontigenin Babu et al. (2004)
24 Piceatannol Liu et al. (2007), Wang et al. (2010)
25 Piceatannol-3 -O-␤-d-glucopyranoside Wang et al. (2010)
26 Piceatannol-4 -O-␤-d-(6 -O-galloyl)-glucopyranoside Liu et al. (2007)
27 Piceatannol-4 -O-␤-d-(6 -O-p-coumaroyl)-glucopyranoside Wang et al. (2010)
28 Piceatannol-4 -O-␤-d-glucopyranoside Liu et al. (2007), Wang et al. (2010)
29 Resveratrol Rokaya et al. (2012)
30 Rhapontigenin Babu et al. (2004)
31 Anthrones 10-Hydroxycascaroside C or anthrone C-glucosides Pradhan et al. (2002), Krenn et al. (2004)
32 10-Hydroxycascaroside D Krenn et al. (2004)
33 10R-chrysaloin 1-O-␤-d-glucopyranoside Pradhan et al. (2002), Krenn et al. (2004)
34 Cascaroside C Krenn et al. (2004)
35 Cascaroside D Krenn et al. (2004)
36 Cassialoin Krenn et al. (2004)
37 Ethers Revandchinone-3 Babu et al. (2003)
38 Revandchinone-4 Babu et al. (2003)
39 Esters Revandchinone-1 Babu et al. (2003)
40 Revandchinone-2 Babu et al. (2003)
41 Asarone ␤-Asarone Babu et al. (2003)
42 Chromones Noreugenin Babu et al. (2004)
43 Flavonoids d-Catechin Liu et al. (2007)
44 Epicatechin Krenn et al. (2003)
45 Carpusin Krenn et al. (2003)
46 Maesopsin Krenn et al. (2003)
47 Carbohydrate Sucrose Wang et al. (2010)
48 Lignan Daucosterol Liu et al. (2007), Wang et al. (2010)
49 Sterol ␤-Sitosterol Liu et al. (2007), Wang et al. (2010)
50 Phenols (+)-Taxifolin Rajkumar et al. (2011a)
51 Daidzein Rajkumar et al. (2011a)
52 Daidzein-8-O-glucoside (Puerarin) Rajkumar et al. (2011a)
53 Flavonol Rajkumar et al. (2011a)
54 Gallic acid Zhou et al. (2011a,b)
55 Quercetin Rajkumar et al. (2011a)
56 ␤-Resorcylic acid Rajkumar et al. (2011a)
57 Inorganic elements Aluminum, bromine, calcium, carbon, chlorine, cobalt, copper, Hameed et al. (2008), Singh et al. (2010), Haq and Ullah (2011)
iron, lithium, magnesium, manganese, oxygen, phosphorus,
potassium, silicon, sodium, sulfur, thallium, titanium, zinc

gram negative (Klebsiella aerogenes, Chromobacterium violaceum against different filamentous fungi and bacteria. The extract inhib-
and Pseudomonas aeruginosa) bacteria. Revandchinone-1 and 3 had ited the growth of Shigella dysenteriae (responsible for dysentery in
lower degrees of antibacterial activity (inhibition zone diameters humans) but not other bacteria (Staphylococcus aureus, Salmonella
of 7–9 mm for the 30 and 100 ␮g/ml test concentrations) than did typhimurium, Salmonella paratyphi, Salmonella typhi, Escherichia coli
revandchinone-4, with an inhibition zone diameter of 12–14 mm and Pseudomonas aeruginos). For fungi, the inhibition of growth
at both the 30 and 100 ␮g/ml test concentrations (Babu et al., was the highest for Fusarium chlamydosporum, followed by
2003). In another experiment, Aqil and Ahmad (2003) investigated Trichoderma viride, Rhizoctonia bataticola, Aspergillus niger and
the effects of the ethanolic extracts of Rheum australe rhizomes Alternaria alternata.
772 M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774

4.4. Anti-inflammatory activity immuno-enhancing effect via Th-1 and Th-2 cytokine regulation
in vivo (Kounsar et al., 2011).
Chauhan et al. (1992) studied the anti-inflammatory effect of the
methanol extract of the Rheum australe rhizome (500 mg/kg). The 4.8. Nephroprotective activity
anti-inflammatory activity was evaluated by using carrageenan-
induced paw oedema. It was found that the degree of inhibition of The nephroprotective activity of the methanolic water-soluble
oedema increased with time, reaching maximum inhibition after (W-S) and water-insoluble (W-INS) extracts of the Rheum australe
5 h. This inhibitory activity was comparable to the control drug rhizome against chemical-induced (cadmium chloride, mercuric
Ibuprofen (50 mg/kg body weight). chloride, potassium dichromate and gentamicin) kidney damage
in rats was determined. The MeOH W-S extract exhibited a better
4.5. Antioxidant activity nephroprotective effect on all the segments (S1, S2 and S3) of the
proximal tubule of kidney against cadmium-, mercury- and potas-
The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical sium dichromate-induced nephrotoxicity in rats. W-INS extracts
scavenging activities, inhibitory effects on lipid peroxidation (LPI) were found to have a protective effect on the S2 segment of the
and Fe3+ reducing antioxidant properties of methanolic/aqueous proximal tubule only when nephrotoxicity was induced by cad-
extracts of the Rheum australe rhizome were studied. Although the mium chloride and mercuric chloride (Alam et al., 2005).
aqueous extract was inferior to the methanolic extract in effec-
tiveness, both extracts showed significant antioxidant potential 5. Toxicity
in a dose-dependent manner (P < 0.05). Furthermore, the extracts
proved to contain a high number of phenolic compounds, which When reviewing different types of literature, we did not dis-
were found to have strongly significant positive correlation with cover any information that detailed any adverse effect or toxicity
free radicals (DPPH and OH) scavenging efficacies, percentages of resulting from Rheum australe consumption in humans. However,
lipid peroxidation (LPI) and Fe3+ reductions (P < 0.05) (Rajkumar some of the literature mentioned precautions that should be taken
et al., 2011a). Testing the free radical scavenging capacity of dif- when using Rheum australe (DPR, 2007; Khare, 2007). Consump-
ferent compounds extracted from the Rheum australe rhizome in tion of the Rheum australe rhizome, which tastes sour and bitter,
combination with DPPH (100 ␮M solution) determined that only is not recommended for people who have tendencies toward gout,
carpusin or marsupsin and maesopsin have significant antioxidant rheumatism, epilepsy or any uric acid diseases or for people with a
activity, whereas chrysophanol, physcion and emodin as well as history of renal or gall bladder stones (Web 1 and 2). The rhizome
their 8-O-glucosides were found to be inactive (Krenn et al., 2003). contains some oxalic acid, which, when consumed, can combine
with calcium in the blood to form insoluble calcium oxalate crys-
tals that may be deposited in the kidneys or gall bladder (DPR,
4.6. Hepatoprotective activities 2007; Khare, 2007). The leaves of the plant are generally not recom-
mended for human consumption due to higher oxalic acid content
The protective effects of the ethanolic extracts of the Rheum and are nephrotoxic or corrosive in nature. In addition, it is believed
australe rhizome on carbon tetrachloride (CCl4 )-induced rat liver that another unidentified toxic substance, commonly known as
cell injury have been evaluated. Primary cultures of rat hepato- senna glycosides, is present in the leaves (Web 2).
cytes (6, 12, and 24 h culture) treated with ethanolic extracts (10,
50 and 100 ␮g) showed LDH and GPT release in a concentration-
dependent manner, thus indicating hepatoprotective activity. The 6. Conclusion
hepatoprotective activity of the same ethanolic extract (EtOH)
against CCl4 -induced liver damage in Wister rats was determined. The available scientific research on Rheum australe has shown
Carbon tetrachloride administration caused a significant increase that it is an important medicinal plant used in a wide range of eth-
in the serum activities of AST, ALT and ALP and a similar increase in nomedical treatments, especially for constipation, stomachache,
the total bilirubin. Oral administration of Rheum australe at 3.0 g/kg, dysentery, blood disorders, broken or fractured bones and sprains.
p.o. significantly decreased the above elevated parameters, and the Although it has been reported that Rheum australe might be slightly
normal structure of the liver pattern was restored (Ibrahim et al., toxic (DPR, 2007; Khare, 2007), the plant has been in use for a long
2008). In a different experiment, the hepatoprotective effects of a period of time without any documented serious adverse effects.
methanolic extract (0.6 g/kg) and an aqueous extract (equivalent to The detailed information presented in this review provides evi-
2 g/kg) of Rheum australe against paracetamol-induced liver dam- dence for its various traditional uses. The pharmacological studies
age in Wister rats were examined. The aqueous extracts did not that have tested the validity of traditional uses confirmed its anti-
significantly affect serum enzymes, albumin and bilirubin levels. fungal, anti-inflammatory, antimicrobial and immuno-enhancing
However, the methanolic extract was effective and comparable to activities and support the use of Rheum australe to increase renal
the control drug silymarin (50 mg/kg) and the other simultaneously functions. Reports of the use of this plant for the same ailments
tested Unani herbal medicine, akseer-e-jigar (1 g/kg) (Akhtar et al., in different areas and countries indicate that the plant is of huge
2009). biological importance.
Rheum australe contains different types of secondary com-
pounds that have different structural characteristics with different
4.7. Immuno-enhancing activity pharmacological effects. Different compounds (rhapontigenin,
desoxyrhaponticin, desoxyrhapontigenin, chrysophanol-8-O-␤-
A study of the effects of the ethyl acetate extracts of Rheum d-glucopyranoside and torachrysone-8-O-␤-d-glucopyranoside)
australe rhizome has shown immuno-enhancing activity in murine have been shown to inhibit yeast ␣-glucosidase and mammalian ␣-
macrophage cell lines. The results revealed that there was a dose- glucosidase. Chrysophanol and revandchinone-1, 3 and 4 exhibited
dependent increase in the release of NO (nitric oxide) and the antibacterial and antifungal activities. Phenolic compounds have
cytokines TNF-a and IL-12 and a decrease in IL-10 in RAW 264.7 successfully proven themselves as antioxidants. The traditional use
macrophage cell lines in the presence of the extract alone. These of the plant for the treatment of dysentery has been supported
effects indicate that the Rheum australe ethyl acetate extract has an by the observation that the crude extract inhibited the growth of
M.B. Rokaya et al. / Journal of Ethnopharmacology 141 (2012) 761–774 773

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R.P., Subedi, B.P., Vetaas, O.R., Ase, T.H. (Eds.), Vegetation and Society: Their Inter-
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are required, especially on the isolated compounds in vivo, in vitro of Bergen, Norway, pp. 83–97.
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project no. RVO 67985939. We are thankful to Michael Heinrich and Conservation of plant resources, community development and training in
the other three anonymous reviewers for their useful comments on applied ethnobotany at Shey-Phoksundo national park and its buffer zone,
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