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Holarrhena antidysenterica Wall. ex DC.

Synonyms

Chonemorpha antidysenterica (Roth) G.Don, Chonemorpha pubescens (Wall.) G.Don, Echites adglutinatus Burm.f., Echites antidysentericus Roth, Echites antidysentericus Roxb. ex Fleming [Invalid], Echites pubescens Buch.-Ham. [Illegitimate], Elytropus pubescens (Wall.) Miers, Holarrhena antidysenterica (Roth) Wall. ex A.DC., Holarrhena antidysenterica Wall. [Invalid], Holarrhena codaga G.Don, Holarrhena febrifuga Klotzsch, Holarrhena fischeri K.Schum., Holarrhena glaberrima Markgr., Holarrhena glabra Klotzsch, Holarrhena macrocarpa (Hassk.) Fern.-Vill., Holarrhena malaccensis Wight, Holarrhena perrotii Spire, Holarrhena pierrei Spire, Holarrhena tettensis Klotzsch, Holarrhena villosa Aiton ex Loudon, Nerium sinense Hunter ex Ridl., Physetobasis macrocarpa Hassk. [23]

Vernacular Names

English Fever pod, holarrhena, kurchi bark, tellichery bark [2]
India Kurchi, kura, kutaja, tiptaka, indrajau [1]
France Ecorce de conessie [2]
Portugal Quine, erva do Malabar [2]
East Africa Mti mweupe, mkwale (Swahili) [2].

General Information

Description

Holarrhena antidysenterica is a member of the Apocynaceae family. It is a small deciduous tree that reaches up to 6 m high. The bark is grey, exfoliating and smooth outward and exudes abundant white latex in all parts. The leaves are opposite ovate-oblong with entire margins and pale-green in colour. The leaves measure 1.5-20 cm x 1.5-11 cm with cuneate or rounded base and apex acuminate to acute, shortly hairy to glabrous. The veins are pinnate with 5-25 pairs of lateral veins. The stipules are obscure. The petiole is 1 cm long, shortly hairy and glandular at base. The flowers are white and fragrant. Fruits are 30 cm long and appear in pairs, cylindrical, dark grey with white specks all over. The seeds are 1 cm long with 2-2.5 cm long hair at the top [1] [2].

Plant Part Used

Bark and seeds [1].

Chemical Constituents

Antidysentericine, conarrhimin, conamine, conesimine, conessine, conimine, conkurchine, holadysenterine, holamine, holantosines A and B, holaphylline holaphyllamine, holarrenine, holarrhemine, holarrhimine, holarrhine, holarrhinine, isoconessimine, kuchicine, kurchamine, kurchessine, kurchine, kurcholessine, lettocine, norconnesine [1] [2] [19] [20] [21].

Traditional Uses

Barks are considered astringent, anthelmintic, stomachic, febrifuge, bitter, antidysenteric, and tonic [2] [3]. The bark has been used to treat amoebic dysentery, piles, anaemia, asthma, bronchopneumonia, dropsy, dysuria, influenza, rheumatism, toothache, vomiting, nausea, intestinal worms, dyspepsia, chest complains and skin and spleen diseases [1]. Barks of the stem and roots can be administered orally to treat amoebic dysentery while a hot decoction of the stem bark is gargled to treat toothache [2]. The fresh bark was suggested to be used to treat acute dysentery [4].

Leaves pounded in water are used by Kenyans to treat stomachache [2].

Seeds of H. antidysenterica are considered cooling, astringent, febrifuge, digestive, bitter, carminative, antidysenteric, antiperiodic, aphrodisiac, expectorant, conceptive, anthelmitic and antidote to poison [1] [3]. The seeds can be used as antiperiodic when combine with other antiperiodic such as Cocculus cordifolius. Apart from that, Arabic and Persian writers considered the seeds as lithontriptic, aphrodisiac and tonic [3].

Roots boiled in milkare used as an antidote to snakebite and to treat venereal diseases. Infusion of the roots is used to stimulate milk production. In southern Africa, the infusion of the powdered roots is prescribed for constipation, abdominal pains, asthma, infertility, aphrodisiac, and to induce abortion [2].

The powdered roots and leaves are used to arrest post-partum bleeding and nose bleeding. In India the bark and leaves are topically applied over piles, scabies, boils and ulcers [2].

Preclinical Data

Pharmacology

Anti-urolithic activity

The crude aqueos-methanolic extract of H. antidysenterica (0.3 mg/mL) was found to have ability to decrease the size of crystals of calcium oxalate monohydrate (COM) and transformed it to calcium oxalate dehydrate (COD) by significantly (p < 0.05) reducing the cell toxicity and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm (2)) crystals. The same extract (30-100 mg/kg) prevented toxic changes in male Wistar rats given lithogenic agents (ethylene glycol 0.75 % and ammonium chloride 1) for 21 days.  The antilitholithic activity is probably due to anti-aggregation and renal epithelial cell protective activity it may possessed [5].

Antidiarrhoeal activity

Hydro-ethanol crude extract of H. antidysenterica (0.01-3.0 mg/mL) studies on the antidiarrhoeal activity of the plant proved to be positive as having gut stimulant and relaxant activities. The extract was found to initially stimulate smooth muscle contractions at low dose and cause relaxation at a higher concentration. It was found to inhibit high K+-induced contraction at concentration range of 0.01-1.0 mg/mL and shifted Ca++ concentration response curves to the right. The implication is that this is possibly mediated through activation of histamine receptors and Ca++ channel blockade  [6].

Antidiabetic activity

Hydro-methanol (2:3) extract of H. antidysenterica seeds (200, 400 and 800 mg/kg) administered orally to starch (6 g/kg) treated rats showed antidiabetic activity by significantly (p <0.05) reduced the blood glucose level with no significant variation compared to control group treated with only starch in isotonic saline solution for 400 and 800 mg/kg extract. The extract also inhibit the intestinal α-glucosidase rat intestinal supernatant in a dose dependent manner (IC50 0.52 mg/mL) compared to standard acarbose [7].

Immunomodulatory activity

H. antidysenterica was found to have the ability to stimulate phagocytic function and inhibit humoral component of the immune system [8].

Antimicrobial activity

Antibacterial activity

The crude methanol extract of the bark of H. antidysenterica was active against Staphylococcus aureus, S. epidermidis, Streptococcus faecalis, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. Chemical fractionation indicated the alkaloid portion was the most active against the bacteria especially S. aureus. There is also evidence that the ethanolic extract of the bark is effective against anti-methicillin-resistant S. aureus (MRSA) and extended spectrum beta-lactamases (ESbetaL)-producing E.coli  [9] [10] [11] [12] [13] [14] [15].

Antimalarial activity

Chloroform extract of H. antidysensterica showed in vitro antiplasmodial activity (IC50 5.5 μg/mL) using pLDH assay and ED50 value 18.29 mg/kg in Plasmodium berghei NK65 stain infected Swiss albino mice. The extract (30 mg/kg) also significantly reduced the parasitaemia in mice by 73.2 %  [16].

Anticholinesterase activity

Five steroidal alkaloids were found to have anticholinesterase activity (conessine, conessimin, conarrhimin and conimin) with the most potent is conessimin with an IC50 value 4 μM  [19].

Toxicities

In screening of 50 medicinal plants for the content of pyrrolizidine alkaloids, H. antidysenterica was amongst the 3 species that showed positive presence of the compounds. Rats fed with H. antidysenterica showed evidences of liver toxicity which are disruption of the centrilobular veins, congestion or haemorrhage in the centrilobular sinusoids, centrilobular or focal hepatocellular necrosis compatible with the action of pyrrolizidine alkaloids [17].

Teratogenic effects

No documentation

Clinical Data

Clinical Trials

40 cases of amoebiasis and/or giardiasis were treated with H. antidysenterica bark extract. 70% of the cases that showed good response were Entamoeba histolytica cyst passers [18].

Adverse Effects in Human:

No documentation

Used in Certain Conditions

Pregnancy / Breastfeeding

No studies had been done on its abortifacient activity. The fact that it had been used to procure abortion in some African society, warrants a cautionary note on its use during pregnancy. However, there should not be any problem of its use during lactation being a lactagogue itself [1] [2] [3].

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

The antidiabetic activity found in the plant makes it unsuitable to be used with antidiabetic drugs [7].

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

References

  1. Chauhan NS. Medicinal and aromatic plants of Himachai Pradesh. New Delhi: Indus Publishing;1999. p. 225-228.
  2. Schmelzer GH, Fakim AG. Medicinal plants 1.  Wageningen: PROTA Foundation;  2008. p. 332.
  3. Nadkarni KM. Dr. K. M. Nadkarni’s Indian material medica Volume 1. New Delhi: Popular Prakashan; 1996. p. 636.
  4. Burkill IH. A Dictionary of economic products of the Malay Peninsula Volume 1. Kuala Lumpur: Ministry of Agriculture and Cooperatives Malaysia; 1966. p. 1199-1200
  5. Khan A, Khan SR, Gilani AH. Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica. Urol Res. 2012 Dec; 40(6):671-81. doi: 10.1007/s00240-012-0483-1. Epub 2012 May 24.
  6. Gilani AH, Khan A, Khan AU, Bashir S, Rehman NU, Mandukhail SU. Pharmacological basis for the medicinal use of Holarrhena antidysenterica inmotility disorders. Pharm Biol. 2010 Nov;48(11):1240-6. doi: 10.3109/13880201003727960. Epub 2010 Sep 7.
  7. Ali KM, Chatterjee K, De D, Jana K, Bera, TK, Ghosh. Inhibitory effect of hydro-methanolic extract of seed of Holarrhena antidysenterica on alpha-glucosidase activity and postprandial blood glucose level in normoglycemic rat. Journal of Ethnopharmacology. 2011 March 6;135:194-196.
  8. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I: Preliminary screening. J Ethnopharmacol. 1986 Nov;18(2):133-41.
  9. Chakraborty A, Brantner AH. Antibacterial steroid alkaloids from the stem bark of Holarrhena pubescens. J Ethnopharmacol. 1999 Dec 15;68(1-3):339-44.
  10. Kavitha D, Shilpa PN, Devaraj SN. Antibacterial and antidiarrhoeal effects of alkaloids of Holarrhena antidysenterica WALL. Indian J Exp Biol. 2004 Jun;42(6):589-94.
  11. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant extracts on clinical isolates of beta-lactamase producing methicillin resistant Staphylococcus aureus. J Basic Microbiol. 2005;45(2):106-14.
  12. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal plants against ESbetaL-producing multidrug-resistant enteric bacteria. Microbiol Res. 2007;162(3):264-75. Epub 2006 Jul 27.
  13. Aqil F, Ahmad I, Owais M. Evaluation of anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and synergy of some bioactive plant extracts. Biotechnol J. 2006 Oct;1(10):1093-102.
  14. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian medicinal plants. Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):79-92.
  15. Kavitha D, Niranjali S. Inhibition of enteropathogenic Escherichia coli adhesion on host epithelial cells by Holarrhena antidysenterica (L.) Wall. Phytother Res. 2009 Sep;23(9):1229-36. doi: 10.1002/ptr.2520.
  16. Verma G, Dua VK, Agarwal DD, Atul PK. Anti-malarial activity of Holarrhena antidysenterica and Viola canescens,traditionally used against malaria in the Garhwal region of north-west Himalaya. Malar J. 2011 Feb 2;10:20. doi: 10.1186/1475-2875-10-20.
  17. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies on medicinal plants of Sri Lanka: occurrence of pyrrolizidine alkaloids and hepatotoxic properties in some traditional medicinal herbs. J Ethnopharmacol. 1981 Sep;4(2):159-77.
  18. Singh KP. Clinical studies on amoebiasis and giardiasis evaluating the efficacy of kutaja (Holarrhena antidysenterica) in entamoeba histolytica cyst passers. Anc Sci Life. 1986 Apr;5(4):228-31.
  19. Yang ZD, Duan DZ, Xue WW, Yao XJ, Li S. Steroidal alkaloids from Holarrhena antidysenterica as acetylcholinesterase inhibitors and the investigation for structure-activity relationships. Life Sci. 2012 Jun 14;90(23-24):929-33. doi: 10.1016/j.lfs.2012.04.017. Epub 2012 Apr 30.
  20. Janot MM, Khuong-Huu Q, Monneret C, Kaboré I, Hildesheim J, Gero SD, Goutarel R. Alkaloidal steroids-C. Holantosines A and B, new amino-glyco-steroids isolated from leaves of Holarrhena antidysenterica (Roxb.). Wall. (Apocynacées). Tetrahedron. 1970 Apr;26(7):1695-709.
  21. Kumar A, Ali M. A new steroidal alkaloid from the seeds of Holarrhena antidysenterica. Fitoterapia. 2000 Apr;71(2):101-4.
  22. Kumar N, Singh B, Bhandari P, Gupta AP, Kaul VK. Steroidal alkaloids from Holarrhena antidysenterica (L.) Wall. Chem Pharm Bull (Tokyo). 2007 Jun;55(6):912-4.

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