50 | P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 6(1): January-February 2017 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES IMPACT FACTOR 2.96*** ICV 6.16*** Pharmaceutical Sciences REVIEW ARTICLE …………!!!

CHONEMORPHA FRAGRANS: A PHARMACOLOGICAL UPDATE Mathew George, Lincy Joseph, Sujith K, Minu Mathew* Pushpagiri College of Pharmacy, Thiruvalla-689107, Kerala, India.

KEYWORDS: ABSTRACT In the present review, an attempt has been made to congregate the Medicinal Properties, botanical, morphological phytochemical, ethnomedicinal and fragran, pharmacological information on Herb, Pharmacological (Moon)Alston, a medicinal herb used in the indigenous system of Activities. medicine. It has been adored in almost all ancient ayurvedic texts For Correspondence: for its extraordinary medicinal properties. It is sweet and astringent Minu Mathew * in taste. The roots of chonemorpha possess several medicinal Address: properties. Ayurvedic texts categorise chonemorpha is used as Pushpagiri College of carminative, anthelmintic and digestive. While alleviating kapha Pharmacy, Thiruvalla- and vata, it aggravates pitta. Chonemorpha fragrans(Moon)Alston 689107, Kerala, India. has a variety of biological / pharmacological activities such as

antiamoebic, antipyretic, antidiabetic, anti parasitic, anthelmentic,

anticancer, HIV disorder, skeletal muscle relaxant and

gynaecological disorder . This review will definitely help for the

researchers as well as clinicians dealing with chonemorpha fragran

to know its proper usage as this herb is seemed to be highly

valuable, possessing many pharmacological / medicinal properties.

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INTRODUCTION: Chonemorpha fragrans is a medicinal used in Indian medicinal systems. Entire plant, roots and the root bark are used for fever and stomach disorders. The trade is mainly confined to Kerala state under the name Perumkurumba and the dried roots are sold commercially. In Mizoram, the plant is used for treatment of gynaecological disorders .C. fragrans, has been included in the list of threatened medicinal . It is known to possess muscle relaxant and antiparasitic properties. Phytochemical analysis of C. fragrans has revealed the presence of steroidal , like chonemorphine and funtumafrine. Camptothecin, a well known anticancer compound has been reported by us from the ethanolic extracts of the stem bark of C. fragrans collected from Kerala state and also in the callus cultures of C. fragrans. So far, there are no reports on antimicrobial activity and there are scanty reports on secondary metabolite production in vivo and in vitro for this plant. DESCRIPTION[2]

Chonemorpha fragrans belonging to the family, , Chonemorpha fragrans is a stout spreading laticiferous shrub with soft greyish to rusty-brown bark which yields fibre of good quality; leaves simple, opposite, large, orbicular, fulvous to mentose beneath, prominently veined; flower large, whitish to cream-yellow, fragrant, in terminal or pseudo-axillary cymose panicle; fruits long, straight, woody, parallel, follicular mericarps; seeds many, flat, shortly beaked with long white silky coma. The root bark contain 3.03 % of total alkaloids present are japindine,N- formylchonemorphin,N-methyl chonemorphin. Presence of fats, octacosanolceryl alcohol, β – sitosterol and taraxasterol is reported. The leaves and twig contain baurenolacetate and β-sitosterol. The stem yields latex. SYNONYMS :Murva,Morata :Garbhedaro :Manjinaru Telgu :Chaga :Perunkurumpa SCIENTIFIC CLASSIFICATION Kingdom : Plantae Phylum : Division Class :Angiospermae Order : Full Text Available On www.ijupbs.com

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Family :Apocynaceae Genus :Chonemorpha Species :Chonemor phafragrans TRADITIONAL USES[3] The roots are are sweet, bitter, astringent, laxative, thermogenic, depurative, carminative, anthelmintic, digestive, antiscorbutic, anodyne, expectorant and febrifuge. They are useful in vitiate diseases, leprosy, scabies, dyspepsia ,colic, constipation hyperacidity ,cardiac debility, diabetes, jaundice, cough, bronchaitis and intermittent fevers. Murva is used in diseases like anaemia(pandu), fever (jwara), diabetes (prameha), stomach disorders (udararoga), typhoid (visamajwara), urinary infections (asmari) and cough (ksaya) .It is also used in the treatment of diarrhea, polyuria, , leprosy, eye diseases, vomiting and poisoning conditions of vata and kapha, skin diseases, leprosy, scabies, dyspepsia ,colic, constipation hyperacidity ,cardiac debility, diabetes, jaundice, cough, bronchitis and intermittent fevers. CHEMICAL CONSTITUENTS [4] The root bark contain 3.03 % of total alkaloids present are japindine,N-formyl chonemorphin, N- methyl chonemorphin. Chonemorphin dihydrochloride is an antiamoebic principal and show in vitro activity against parasites Entamoeba histolytica (25μg/ml) trichomonas vaginalis (200μg/ml)and in vitro activity against hepatic amoebiasis in golden hamster and intestinal amoebiasis in wealing wistar rats. Presence of fats, octacosanol, ceryl alcohol, β –sitosterol and taraxasterol is reported. The leaves and twig contain baurenolacetate and β- sitosterol. The stem yields latex. It is purgative. PHARMACOLOGICAL ACTIVITY Hepato protective activity[5] There is a lack of reliable hepatoprotective drugs in modern medicine to prevent and treat drug- induced liver damage. Chonemorpha fragrans belonging to family Apocynaceae are used traditionally for their hepatoprotective effect. We wanted to evaluate the hepatoprotective activity of Chonemorpha fragrans and observe whether synergistic hepato-protection exists with silymarin. The in vitro antioxidant and in vivo hepato protective effects of alcoholic extract of Chonemorpha fragrans(C. fragrans) root were evaluated inrats against paracetamol and Isoniazid models. The antioxidant activity of C. fragrans was assayed and activities were compared to standard antioxidant, ascorbic acid. The results revealed that the IC50 values of C. fragrans root extract for DPPH, hydroxyl, superoxide radical scavenging activities were 198.7±0.2, 275.7 ± 0.8 and 177.4±0.4 μg/mL, respectively. Liver injury was induced by paracetamol (2gm/kg) Isoniazid (100

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53 | P a g e International Standard Serial Number (ISSN): 2319-8141 mg/kg) orally for 14 days. The two different set of experiments the Chonemorpha fragrans extracts (200 and 400 mg/kg) and silymarin (25 mg/kg) were administrated orally in preventive models. The Chonemorpha fragrans and silymarin administration prevented the toxic effect of Paracetamol and Isoniazid the biochemical parameters in preventive model. The present study concludes that ethanolic extract of Chonemorpha fragrans root has significant antioxidant and hepatoprotective activity against induced Paracetamol and Isoniazid hepatotoxicity. Antidiabetic activity[6] Ethanolic extract of the roots of Chonemorpha fragrans, a traditionally used antidibetic plant was evaluated for its antihyperglycemic and antihyperlipidemic effect using streptozotocin-nicotinamide induced diabetic rat model. Oral glucose tolerance test with 2g/kg of glucose and normoglycemic studies were performed which showed a dose dependant decrease in sugar levels. The acute oral toxicity studies demonstrated the safety of the dose up to 2000mg/kg body weight. The diabetic rats were treated with ethanolic root extracts, at a dose of 200mg/kg and 400mg/kg based on the acute toxicity study. Standard groups were treated with Glibenclamide at a dose of 0.6mg/kg. Treatment was continued for 21 days and the weights of the rats and serum glucose levels were measured on 1st,7th,14th and 21stday. Other biochemical parameters like lipid profile, HbA1c, ALT, AST, serum creatinine, urea and total proteins were evaluated on the last day of the study. The results of the study have shown a significant difference between the initial and final fasting blood glucose levels of C. fragrans and glibenclamide treated diabetic rats. These results justify the traditional claim of the usefulness of C. fragrans root extract in the treatment of type 2 D. mellitus. Antiamoebic activity[7] In a bioassay-directed screening programme of plants for the identification of active constituents the steroid “Chonemorphine” was isolated and identified as the antiamoebic and antitrichomonad principle of Chonemorpha fragrans. Antipyretic activity[8] Murva is one of the controversial drugs used in Ayurvedic medicine. In the present study two botanical sources of Murva, viz. Wattakakavolubilis and Maeruaob longifolia, were tested for antipyretic activity by yeast-induced pyrexia in Wistar albino rats. Alcohol and aqueous extract of both species significantly reduced the elevated rectal temperature in febrile rats within 30 min of their administration. The results of these studies support the traditional use of these two botanical sources of the drug Murva in the treatment of fever.

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Anti-parasitic agent[9] Chonemorphines, a steroidal isolated from Chonemorpha fragrans Moon (Apocyanaceae) was identified as an antimoebic principle during the course of a screening programme for novel antiparasitic agents from plant sources. At a dosage of 100 mg/kg x 4 chonemorphineled to a 100% cure of experimental hepatic infection in golden hamsters and cleared 90% of the intestinal infection in weanling Wistar rats at 200 mg/kg (x4) dosages. The discovery of chonemorphine as an antiamoebic agent is an addition to the few known plant amoebicides such as emetine and conessine. Skeletal muscle relaxant[10] Skeletal muscle relaxant property of Chonemorpha macrophylla(CM). The skeletal muscle relaxant effect of the alcoholic extract of CM was studied on isolated frog rectus abdominis muscle, isolated rat phrenic nerve diaphragm muscle preparation and in intact young chicks. The parameter studied in the isolated muscle or isolated nerve muscle preparations was the extent of inhibition of acetylcholine or electrically-induced contraction of skeletal muscles. In intact chicks, the drug was administered i.v. in wing veins and the onset, duration and nature of paralysis were recorded. In all the experiments, the effect of the drug was compared with that of gallamine and succinylcholine. The alcoholic extract of CM reduced the acetylcholine-induced contraction of isolated frog rectus abdominis and electrically stimulated contractions of rat phrenic nerve diaphragm in a dose- dependent manner. In un anaesthetized chicks, it produced spastic type of paralysis with extension of the neck and limbs. The effects were similar to the effects of succinylcholine but different from those of gallamine. The alcoholic extract of CM possesses skeletal muscle relaxant property. It produces depolarizing type of muscle paralysis similar to that produced by succinylcholine. Anthelmintic activity[11] Roots of Chonemorpha fragrans belonging to family Apocynaceae showed the anthelmintic activity. Anticancer activity[12] Camptothecins are one of the most important anticancer alkaloids of the 21stcentury because of their clinical applications against cancer, HIV Chonemorpha fragrans (C. fragrans), a liana belonging to family Apocynaceae, shows presence of widely used anticancer compound Camptothecin (CPT). CPT is a modified monoterpeneindole alkaloid produced by very few species belonging to unrelated orders of angiosperms, especially plants belonging to the families Apocynaceae and Icacenaceae. A sensitive high performance thin layer chromatography method (HPTLC) was used for detection and quantification of CPT. HPTLC analysis showed that highest

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55 | P a g e International Standard Serial Number (ISSN): 2319-8141 amount of CPT was present in root methanolic extract (0.023% of dry weight) followed by stem bark methanolic extract (0.013% of dry weight). Also, the subcellular localization of an anticancer drug has been studied using autofluroscence property of CPT under Ultra violet (UV) light. Localization study revealed that out of all the organs studied roots accumulated highest levels of CPT followed by stem bark. Xylem tissues showed a major accumulation site for CPT. Presence of CPT in in vitro culture is an important finding as in vitro systems can be used for further experiments to reduce overexploitation of natural population. This is the first report regarding subcellular localization and quantification of CPT in sequential extracts of different plant parts in C. fragrans. Gynaecological disorder[13] In Mizoram, the plant is used for treatment of gynaecological disorders. C.grandiflora, has been included in the list of threatened medicinal plants. Antibacterial Activity[14]: Antibacterial activity of ethanolic extracts of C. grandiflora, was tested against Bacillus subtilis (ATCC 6633) Salmonella typhae and Klebsiella pneumonae, procured from NCIM, NCL, Pune and Department of Biotechnology, Sinhagad College, Pune. Ethanolic extracts of stem with bark and leaf callus, were prepared by adding ethanol to the residues, to get the concentration 250 ppm and 500 ppm respectively. Nutrient agar medium was prepared. Bacterial cultures were inoculated into nutrient broth and incubated at 35±2°C. After 24 hours, the bacterial suspension was centrifuged at 6000 rpm for 15 min. The pellet was suspended in sterile distilled water and the transmittance of suspension was corresponding to 70- 80% at 530 nm and a constant number 10 6 cells/ml. 0.1 ml of suspension was spread on the plates. The wells were prepared by using 0.6 mm borer and 5 wells were prepared in each petridish. 75µl of extract was loaded in each well. The solvent ethanol was kept as a negative control and the standard antibiotic Cephotaxime (250 and 500 ppm respectively) was used as a positive control. 3 replicates were kept for each set of experiment and each set was repeated twice. Inhibition zone was recorded in mm after 24 hours. Antioxidant potential and DNA protection ability[15] Chonemorpha fragrans(Moon) Alston is a liana belongs to family Apocynaceae. Due to its ethanobotanical importance, it is used in traditional medicinal systems as a part of various medicinal preparations. In the work presented here the plant has been explored for its antioxidant potential and DNA protection ability. The antioxidant potential of C. fragrans was determined using DPPH, FRAP, Phosphomolybdanum and H2O2 Scavenging Capacity. Phenol and flavonoid content was measured followed by Correlation analysis between antioxidant activities and phenols

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56 | P a g e International Standard Serial Number (ISSN): 2319-8141 and flavonoid content. In addition, DNA protection ability of extracts was evaluated using double stranded plasmid DNA. C. fragrans extracts have shown significant antioxidant potential. Phenol content showed high correlation with Phosphomolybdenum reduction potential where as flavonoid content with Phosphomolybdenum as well as H2O2 radical scavenging potential. All the extracts exhibited an ability to protect the DNA against devastating effects of Fentons reagent except methanol roots, stem bark, in vitro and callus extracts. The extracts have shown significant antioxidant activity and Phenol, flavonoid content was found to contribute towards antioxidant potential of C. fragrans. The extracts also showed the DNA protection potential pointing toward its pharmaceutical importance. Conclusion Chonemorpha fragrans, the versatile medicinal plant is the unique source of various types of compounds having diverse chemical structure. Very little work has been done on the biological activity and plausible medicinal applications of these compounds and hence extensive investigation is needed to exploit their therapeutic utility to combat diseases. A drug development programme should be undertaken to develop modern drugs with the compounds isolated from Chonemorpha fragrans. Present review spotlights the classical antidiabetic, anticancer, immunomodulatory, antioxidant, antimicrobial, antitoxic claims of Chonemorpha fragrans and their validation by contemporary researches. For the last few years, there has been an increasing trend and awareness in medicinal plants research. Quite a significant amount of research has already been carried out during the past few decades in exploring the chemistry of different parts of Chonemorpha fragrans. While Chonemorpha fragrans has been used successfully in Ayurvedic medicine for centuries, an extensive research and development work should be undertaken on Chonemorpha fragrans and its products for their better economic and therapeutic utilization. This review can be used for further research as well as clinical purpose. REFERENCES: 1. V. Kulkarni1, A. A. Patwardhan2, A. S. Upadhye3 and N. P. Malpathak, Pharmacognostic evaluation of chonemorpha grandiflora, an endangered medicinal plant, International Journal of Pharmaceutical Sciences And Research. 2. Chandraamrish , Rajputrekha, Chonemorpha Fragrans, An Endangered Medicinal Plant: A Review International Journal of Pharmaceutical EruditionNov. 2011, 1(3), 10-16 10. 3. The Wealth of India ,A dictionary of Indian raw materials and industrial products, the wealth of India, raw materials Volume-3: Ca-Ci, Revised Edition, Publication and Information Directorate, Council of Scientific and Industrial Research ,New Dehli,India-1992:486.

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4. Ram P. Rastogi and B. N. Mehrotra, Compendium of Indian Medicinal Plants, Volume-I, National Institute of Science Communication and Information Resources, Council of Scientific and Industrial Research, New Dehli,India-1960-1969:99. 5. M. Duraisankar, Manjula Devi, P. Shanmugasundram, Hepatoprotective activity of alcoholic extract of Chonemorpha fragrans root in against Paracetamol and Isoniazid- induced liver damage in rats International Journal of PharmTech Research vol 8. 6. Bobby s. prasad , K. K. srinivasan and Jyotiharindran, chonemorpha fragrans (moon) alston an effective antihyperglycemic and antihyperlipidemic agent in streptozotocin nicotinamide induced diabetic rats IJPSRR (2016), vol. 7, issue 3. 7. Potsmesil, M. Camptothecins: From Bench Research to Hospital Wards Cancer Research1994;54:1431-1439. 8. Chatterjee DK, Iyer N, Ganguli BN, Antiamoebic activity of chonemorphine, a steroidal alkaloid, in experimental models, Parasitol Research, 1987;74(1):30-3. 9. VinayJaiswal, Sandeep Gupta, Anujkumar, SaherJafer, Swati Mittal,Overview on medicinal plant used in anthelmintic,DrugInvention Today 2011,3(5),57-61. 10. Roy Ranendra Kumar, Ray NM., Das AK, Skeletal muscle relaxant effect of Chonemorphamacrophylla in experimental animals,Indian Journal of Pharmacology, March- April, 2005,37(2): 116-119. 11. Potsmesil, M. Camptothecins: From Bench Research to Hospital Wards Cancer Research1994;54:1431-1439. 12. Pradnya Kedari, Nutan Malpathak,Subcellular Localization and Quantification of Camptothecin in Different Plant Parts of Chonemorpha Fragrans Advances in Zoology and Botany 1(2): 34-38, 2013. 13. Sarah Khan, N. Mohan Karnat, Darshan Shankar. India's foundation for revitalization of local health traditions, pioneering In Situ conservation strategies for medicinal plants and local cultures, Herbalgram, 2005; 68: 34-45. 14. V. Kulkarni, A. A. Patwardhan, A. S. Upadhye and N. P. Malpathak, Pharmacognostic evaluation of chonemorpha grandiflora, an endangered medicinal plant. IJPSR. 15. Pradnya Kedari and Nutan Malpathak, Exploring antioxidant activity and DNA protection potential of chonemorpha fragrans IJPSR (2014), vol. 5, issue 12.

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