Review Article SpatulaDD.2015;5(3):133-138 Bio-efficacy and Phyto-Pharmacological Activities of Aristolochia Indica Aristolochia Indica’nın biyoetkinliği ve fitofarmakolojik aktivitesi Sandeep V. Binorkar1, Gajanan R. Parlikar2, Anand B. Kulkarni3 1 Dept. of Agadatantra, Govt. Ayurveda College, Vazirabad, Nanded, Maharashtra state, India 2 Ayurveda Extension Officer, Zilla Parishad, Sangli, India 3 Dept. of Agadatantra, Bharatiya Sanskriti Darshan Trust’s Ayurveda Mahavidyalaya & Research Centre, Vishwa shanti dham, Wagholi, Tal. Haveli ABSTRACT Aristolochia indica is a plant genus of the family Aristolochiaceae. The therapeutic value of A. indica has been recognized in different system of traditional medicine including Ayurveda for the treatment of various ailments. A number of Aristolochia species have been used in herbal medicines throughout the world as anti-inflammatory agents for gout, Scorpion stings, arthritis, rheumatism and chronic inflammatory skin diseases. It is also known for the treatment of snakebites. Present article represents the systematic review which was conducted with an objective to search, explore & compile various studies conducted on bio-active compounds isolated from the plant A. indica in respect to its taxonomy, morphology, phytochemistry and pharmacology. Published literature on recent development in researches related to A. indica by scholars in Central Database of Pubmed, various national & international indexed journals including Monographs & Pharmacopeia were reviewed. A. indica one of the most important medicinal herbs used in medication of complementary & alternative medicines because of having a number of pharmacological & Therapeutic properties. Keywords:Aristolochia indica; Ayurveda; Aristolochic acid. ÖZET Aristolochia indica,Aristolochiaceae ailesine ait bir bitki türüdür.Ayurveda dahil geleneksel tıbbın bir çok alanında çeşitli rahatsızlıkların tedavisinde kullanılmaktadır.Aristolochia türlerinin bir kısmı antiinflamatuar ajan olarak gut, akrep sokması, artrit, romatizmal hastalıklar ve kronik inflamatuar deri hastalıklarında bitkisel tedavi edici ajan olarak kullanılmaktadır. Ayrıca, yılan ısırmalarındada kullanılmaktadır. Bu makale, bitkiden izole edilen biyoaktif ajanların kullanıldığı çeşitli çalışmaların incelendiği sistematik bir derlemedir. A. indica’nın sınıflandırılması, morfolojisi, kimyası ve farmakolojisi incelendi. Central Database of Pubmed’te yayınlanan A.indica ile ilgili yazılar ve Monographs & Pharmacopeia gibi ulusal ve uluslararası indekslere giren dergiler bu derlemede kullanılmak üzere tarandı. A. indica çok sayıda farmakolojik ve terapötik özelliklerinden dolayı tamamlayıcı&alternatif tıpta kullanılan çok önemli bir bitkisel ajandır. Anahtar kelimeler:Aristolochia indica; Ayurveda; Aristolochic acid CorrespondingAuthor: Sandeep V Binorkar, Assistant Professor, Dept. of Agadatantra, Govt. Ayurveda College, Vazirabad, Nanded, Maharashtra state, India, Contact No. +91 8888622682 [email protected] INTRODUCTION Nature has bestowed humans and animals with several plants containing number of alkaloids and active principles which cure diseases & promote health. Such medicinal plants are also rich sources to develop potential secondary metabolites. This use of medicinal plant to cure various ailments has been raised from ancient times and transformed from Spatula DD ReceivedOctober 02, 2015; AcceptedNovember 24, 2015 DOI 10.5455/spatula.20151124064158 Published online in ScopeMed (www.scopemed.org). Spatula DD.. generations to generation. In the past decades there is increased attention and interest in use of herbal medicines globally. [1] World Health Organization has enumerated 21,000 plant species utilized around the world for medicinal purpose. [2] In India about 2,500 plants species belongs to more than 1000 genera are being used in the indigenous system of medicine. [3] It as accepted by World Health Organization that 80% of the world population relies 133 Xxx chiefly on traditional medicines involving the use of plant extracts or their active constituents. [4] It has been estimated that in developed countries like US, plant drugs comprises as much as 25% of the total drugs utilized by healthcare sector, while in fast developing countries such as China and India, the contribution is more than 80%. [5] Most of these traditional, ethno-medicinal herbs are utilized without any scientific validations. Therefore such treatments require thorough scientific investigations. Aristolochia indica a one of such shrubs, perennial herbs, twining, belongs to the family Aristolochiaceae. The Aristolochiales are a group of paleoherbs, basal group flowering plants.[6] It is one of the 500 species from the family, documented in Ayurveda and Unani system of medicine as to possess medicinal properties and is used to treat different ailments including snake bites, scorpion stings and envenomation by other poisonous insects. [7,8] It is distributed throughout the tropical, subtropical and Mediterranean countries. In India, plant is found in low hills and planes of south india, west Bengal and some part of north east. It is also available in Nepal, Bangladesh and coromondal coast [9] DISTRIBUTION The species Aristolochia indica is widely distributed in India, Nepal, Sri Lanka and Bangladesh. It is found all over the plains and low hilly part of India especially in tropical and subtropical regions in the low country part from west Bengal, Bihar, Orrisa, Puri, Konkan and majority of districts of south India. It is reported to be endangered species in northern part of India including Gujarat and Rajasthan. [10] MORPHOLOGY It is a slender perennial twinning herb. It is semiwoody having swollen nodes on the stem.[13] Leaves- Variable in size ranging from 3.5 to 1012.5 cm long, simple, alternate, linear oblong to obovate –oblong or sub-panduri form. Undulate margins, base cuneata, rounded, subtruncate or subcordate in shape.[14] Flowers: Flowering and fruiting of this climber are found from the month of December to February.[15] It is few-flowered axillary racemes; bracts are small, ovate, acuminate, opposite the pedicels; 4 cm long having a glabrum pale green inflated [16] thickened above perianth greenish white, Anthers 6 style 6- lobed, capsule 3.8 to 5cm long, bent at a right angle and narrowed into a cylindric tube.[17] Seeds: Deltoid-ovate in shape, acute and flat [3] Roots:Dried root of Aristolochia indica Lin is about 10-25cm long and 1.5–6 cm in diameter, cylindrical, tapers. Externaly it is grayish brown, rough and longitudinally wrinkled and can be easily broken. Inside are starchy, exhibiting alternately greyish brown and whitish radial lines. It is extremely bitter in taste.[18] Transverse section (T.S) of the root showed circular outline with interrupted peripheral cork cells, margin appearing irregular. It is dicotyledonous structure with considerable secondary growth. Cork possessed 7-9 layers of thin walled cells. The vessels were found to be solitary, radially aligned in the centre of the xylem strip. The outer cortex was having 2-3 layers of thick-walled parenchymatous cells consisting reddish brown content.[18] Table 1. Vernacular Name of Aristolochia indica [11,12] Sr. Language No 1 Arabic Name Zaravande 2 Bengali Isarmul 3 English Indian Birthwort 4 Gujarati 5 Hindi 6 Kannada Arkmula, Ruhimula Isharmul, Hooka bel, Isharmul-ki-jar, Isvarmul, Kiramar Isvaberusa, Ishvari balli, Ishwari beru, Gopala putti Thoppalu, Isaraber, Kadula, Kodula, Nanjina baeru, Sapshi, Thoppalu Fig-1. Distribution of Aristolochia indica 134 Spatula DD Binorkar, et al. 7 Malayalam: 8 Marathi 9 Persian Eswaramullu, Garalavegam, Iswaramuli, Perumarunna, Garudakkoti, Careloe-vegon, Carelvevegm, Ishvaramulla, Garalavegam, Garudakkoti, Ishvaramuri, Isvaramurri, Kadalivegam, Karalakam, Karalayam, Karalvekam, Karukappullu, Katalivegam, Perumarunna, Perunkilannu, Perunkilanu, Perunkizhannu Sapasan, Sampsun, Sapsanda, Sapus 13 Tibetan Zaravande Ahigandha, Arkamula, Ishvara, Nakuli, Sunanda, Ahigandha, Gandhanakuli, Garalika, Garudi, Hari, Ishwari, Jovari, Karaleka, Nakuleshtha, Rudrajata, Sunanda, Sunandahari Adagam, Isadesatti, Isura, Isuraver, Karudakkodi, Perumarindu, Adutheendapalai, Adagam, Amutakkoti, Arumaruntu, Arumaruntukkoti, Atakakkoti, Atakam, Chakatikkoti, Chalamiyakkoti, Chalamiyam, Kutuvalli, Ikali, Ikkuramulli, Isadesatti, Isura, Vallikkoti, Vallimoti, Dulagovela, Eswaramulli, Ettakalabanda, Govila, Isvaraveru, Dulagovela, Errakalabanda, Govila, Isvara ven, Nalla Ishwari, Nella Ishvari Na ku li dri z im po 14 Tulu Isaraberu 10 Sanskrit 11 Tamil 12 Telugu Chemical Constituents – The major active principle of the root of Aristolochia indica is aristolochic acid. [19] It also contains essential oil having phenanthrene derivatives like aritolic acid, alkaloid I- curine (aristolochine), sesquiterpenoids like ishwarene, ishwarone, aristolochene, ishwarol, naphthoquinone aristolindiquinone, steriods like Beta-sitosterol, sterol glucoside and others like p-coumaric acid, d-camphor, fixed oil having glycerides and sitosterol. It is having 12-nonacosinoic acid.[13,20] A new sesquiterpene hydrocarbon (I) isolated and characterized as 5β-H, 7β, 10α-selina-4(14), II-diene [21] Spatula DD Fig-2. Parts of Aristolochia indica Fig-3. Leaves and fruits of Aristolochia indica 135 Xxx Fig-8. Aristolochic acid Fig-4. Flowers of Aristolochia indica Fig-9. Aristolactone Fig-5. Seeds of Aristolochia ind Fig-10. Ishwarol Fig-6 & 7. T.S. of Root Portion [18] 136 Spatula DD Binorkar, et al. Fig-11.Ishwarane Chemical constituent of stem oil of the plant analysed by gas chromatography and gas chromatography/mass spectroscopy helped to identify total 15 compounds, the major constituents were trans-pinocarveol (24.2%), a-pinene (16.4%) and pinocarvone (14.2%) [9] Aristololactam N-β- Dglucoside (a phenanthrene derivative) and 3βhydroxy-stigmast-5-en-7-one and 6β-hydroxystigmast-4-en-3-one (steroids) have been isolated.[22] The roots also contain aristolindiquinone, aristolide, 2-hydroxy-1-methoxy-4Hdibenzo quinolone-4,5(6H)-dione, cephradione, aristolactam IIa, stigmastenones II and III, methylaristolate, βsitosterol-β-D-glucoside aristolactam glycoside I, ishwarol, ishwarone, methylaristolate and aristolochene. [3,23,24] Other components found in A. indica include 12-nonacosenoic acid methyl ester, aristolic acid, (12S)-7,12-secoishwaran-12-ol, (+)ledol, ishwarone, methyl aristolate, para-coumaric acid, 5βH,7β,10α-selina-4(14),11-diene, isoishwarane, aristolochic acids I, IVa, aristolochic acid IVa methyl ether lactam and aristolactam β-D-glucoside. [25,26] Ethnomedicinal Uses Root is a tonic, stimulant and emmenagogue. It is also used as an anti-arthritic. [27] Prescribed in pain in abdomen and related bowel troubles of children. A. indica is used as an abortifacient. [3] The root, stem and leaves are the drug of choice for the treatment of snake bite and scorpion- stings. [28][29][30][31][32] Powdered root mixed with honey is used in the treatment of cough, leprosy and ulcers. Powdered root is consumed with water to alleviate fever. Crushed seeds are mixed with water and applied locally to reduce inflammation. Paste prepared from the leaves is also utilized for purpose of alleviating scabies.[33] Juice extracted from the whole plant is used to control diarrhoea. Dried leaves consumed with lukewarm water helps to treat anaemic patient. It also helps in respiratory disorders. [34] The roots & stems of the plant is reported to be used in pains, rheumatism.[35] The plant is also used as an appetiser and aphrodisiac and Tonic.[36][37][38][39] Leaf is antigonorrhoeic, larvicidal and used in eczema on children’s leg and ulcers. The plant is oxytocic. [40] Antimicrobial activity of alcoholic extract of A. indica Linn against various human pathogens including Salmonella typhi, Bacillus subtilis, Staphylococcus aureus and fungal strains like Aspergillus niger, Candida albicans etc have been also reported. [41] Toxicological Concerns LD50 of A. indica is found to be 14.32 mg/kg in mice for Aristolochic acid Methyl ester derivatives. Where as in rats, the oral LD50 of aqueous solutions of aristolochic acids is 203.4 mg/kg bw in males and 183.9 mg/kg bw in females. [42] Intravenous administration is reported to be having LD50 as 82.5 Spatula DD mg/kg bw and 74.0 mg/kg bw respectively. Aristolochic acids are severely nephrotoxic in humans. [14][43][44] It is also been shown to exert potent mutagenic effects in bacterial and mammalian cell systems and persuasive carcinogens in rats and mice at low dose levels. [42][45] DISCUSSION Medicinal herbs are exhibiting a crucial role in treating various disorders since time immemorial. Several existing medicines are directly or indirectly derived from higher plants. Therefore plant derived drugs have an important place in both traditional and modern medicine. A. indica is widely distributed all over India and possesses extreme medicinal values in Ayurveda, Unani, Siddha and other traditional and complementary medicines. Literature review shows that the plan is having potential antimicrobial, antifungal, anti ophidian, cytoprotective and wound healing activity. Ayurveda comprises the holistic approach where as reviewed experimental studies focused on efficacy of isolated individual phytoconstituents. The plant has been used in morbidity of Vata, Pitta & Kapha. It is used as an appetizer, aphrodisiac & anthelmentic. [46] Though A. indica has a number of pharmacologically active components, very few works has been done so far evaluating its efficacy on isolated compounds. Despite of recorded nephrotoxic, anti-fertility and anti-spermatogenic agent, the plant is also used as anti-septic, anti-inflammatory, abortifacient and antiophdian drug. It is also found that Aristolochia indica produce uricosuric effect. [47] Bioassay-guided research including authentic clinical trials could be able to reveal renewable and more persuasive compounds and its efficacy in several ailments from this species. 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