Ghawate V. B. et al. / Journal of Pharmacy Research 2015,9(7),415-418 Review Article Available online through ISSN: 0974-6943 www.jprsolutions.info Pharmacological Activities of Bridelia retusa: A Review

Ghawate V. B.1, 3 *Jadhav V. S.1 and Bhambar R. S.2 1 Department of Pharmacognosy, MES College of Pharmacy, Sonai, Maharashtra, India. 2 Department of Pharmacognosy, MGV’s College of Pharmacy, Panchavati, Nasik, Maharashtra, India. 3 Research Scholar, Bhagawant University, Ajmer, Rajasthan

Received on:25-05-2015; Revised on: 25-06-2015; Accepted on: 25-07-2015

ABSTRACT Bridelia retusa is commonly known as Asana in Marathi. It has long been used in Indian folk medicine to treat broad spectrum of diseases, such as liver diseases, for removal of urinary concretion ,inflammatory diseases etc. Phytochemical studies on Bridelia retusa disclosed major chemical constituents including steroids, triterpenoids, tannins and flavonoids. A research report on Bridelia retusa reveals for its activity, anti-inflammatory activity, hepatoprotective activity, antimicrobial activity, immunomodulatory activity and hypoglycemic effect. Hence in this article, we discuss the biochemical constituents, traditional uses and therapeutic potentials of Bridelia retusa.

KEY WORDS: Bridelia retusa, polyphenols, analgesic, hepatoprotective.

INTRODUCTION: Herbal medicine is still the mainstay of about 75-80% of World popu- It is frequently found in the forests around Gorakhpur and in the lation, mainly in the developing countries for primary health care Western Ghat of South Maharashtra. because of better cultural acceptability, better compatibility with hu- man body and lesser side effects. The chemical constituents present is pungent, bitter, and useful in vata, lumbago and hemiplegia. in them are a part of the physiological function of living flora and The bark is good for removal of urinary concretion. The bark is used hence they are believed to have better compatibility with human body. as liniment with gingelly oil in rheumatism.3 Stem bark powder is Ancient literature also mentions herbal medicine for age related dis- mixed with water given during fever.5 It is also used in jaundice with eases namely memory loss, osteoporosis, diabetic wounds, immune combination with other .6 and liver disorder etc. for which no modern medicine or only palliative therapy is available.1Man has been using herbs and plant products A] Chemical Composition/Key Active Constituents:Antifungal ac- for combating diseases since times immemorial. The Indian subconti- tivity guided fractionation of solvent extracts of the stem bark of nent is enriched by a variety of flora- both aromatic and medicinal Bridelia retusa of the family Euphorbiaceae against Cladosporium plants. This extensive flora has been greatly utilized as a source of cladosporioides, furnished new bisabolane sesquiterpenes, (E)-4-(1,5- many drugs in the Indian traditional system of medicine. In India, the dimethyl-3-oxo-1-hexenyl)benzoic acid, (E)-4-(1,5-dimethyl-3-oxo-1,4- earliest mention of the use of medicinal plants is to be found in Rigveda hexadienyl) benzoic acid, (R)-4-(1,5-dimethyl-3-oxo-4-hexenyl)benzoic which was written between 4500-1600 BC.2 acid and (-)-isochaminic acid, together with the known (R)-4-(1,5-dim- ethyl-3-oxohexyl)benzoic acid (ar-todomatuic acid), 5-allyl-1,2,3- Bridelia retusa is a small or moderate sized deciduous tree up to 7 m trimethoxybenzene (elemicin), (+)-sesamin and 4-isopropylbenzoic acid in height, armed with long conical thorns when young and having (cumic acid). All these compounds showed fungicidal activity on TLC dark brown bark. Exfoliation is irregular flakes, lanceolate or ovate – bioautography method at very low concentrations except elemicin.7 lanceolate leaves, flowers present in long axillary or terminal spikes and greenish yellow fruits.3,4 B] Pharmacological review: *Corresponding author. Ghawate V. B. 1. Antinociceptive, anti-inflammatory and antioxidant activities: Department of Pharmacognosy, MES College of Pharmacy, Antinociceptive and anti-inflammatory potentials of methanolic ex- Sonai, Maharashtra, India. tract of Bridelia retusa fruit (BRME) against different animal models

Journal of Pharmacy Research Vol.9 Issue 7.July 2015 415-418 Ghawate V. B. et al. / Journal of Pharmacy Research 2015,9(7),415-418 was evaluated in rodents. Antinociceptive effects of BRME were 2. Antimicrobial activity: Antimicrobial activity of 10 plant extracts assessed in mice using the acetic acid-induced writhing and formalin and their 34 fractions was evaluated against three sexually transmit- test. Anti-inflammatory effects of BRME in three different doses, ted/reproductive tract pathogens - Neisseria gonorrhoeae, namely, 100, 200, and 400mg/kg, were evaluated by utilizing different Haemophilu sducreyi and Candida albicans. The plant parts were animal models representing various changes associated with inflam- selected; the extracts/fractions were prepared and screened by disc mation, namely, carrageenan-induced paw oedema, histamine and diffusion method. The minimum inhibitory and minimum cidal con- serotonin-induced paw oedema, arachidonic acid-induced paw centrations were determined. The qualitative phytochemical analysis oedema, formalin-induced paw oedema, TPA-induced ear oedema, of selected extracts/fractions showing activity was performed. Out of acetic acid-induced writhings vascular permeability, total WBC count the extracts/fractions tested, three inhibited C. albicans, ten inhib- in paw fluid, and myeloperoxidase assay. The BRME did not exhibit ited N. gonorrhoeae and five inhibited H. ducreyi growth. Study any signs of toxicity up to a dose of 2000mg/kg. The extract showed demonstrated that Terminalia paniculata Roth. extracts/fractions statistical significant inhibition of induced nociception and inflam- inhibited growth of all three organisms. The ethyl acetate fraction of mation in dose dependent manner. The higher dose of extract signifi- Syzygium cumini Linn.and Bridelia retusa (L.) Spreng. Extracts was cantly inhibited pain and inflammation against control (P < 0.001). found to inhibit N. gonorrhoeae at lowest concentrations.12 The present study scientifically demonstrated the antinociceptive Screening methanolic leaf extracts of 21 timber-yielding plants for and anti-inflammatory potential of fruit of B. retusa methanolic ex- antibacterial activity against nine species of uropathogenic bacteria tract. These effects may be attributed to the presence of polyphe- isolated from clinical samples of a hospital (Enterococcus faecalis, nolic phytoconstituents in the extract. Chitosan the flavonoid iso- , Acinetobacter baumannii, Citrobacter lated from the ethanol extract of leaves of Bridelia retusa. Phytochemi- freundii, Enterobacter aerogenes, , cal screening was carried out according to standard procedures from pneumoniae, Proteus mirabilis, and ) by the leaves of Bridelia retusa. The isolated flavonoid was character- the Kirby-Bauer’s disc diffusion method. Two Gram-positive isolates, ized by spectral studies and screened for anti-inflammatory and an- E. faecalis and S. aureus, were resistant to 14 of the 18 antibiotics algesic activity in experimental animal models. The anti inflammatory used. Gram-negative isolates A. baumannii, C. freundii, E. aerogenes, activity was determined by formalin induced paw edema and carrag- E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa were resis- eenan induced paw-edema method, and the analgesic activity was tant to 10, 12, 9, 11, 11, 10, and 11 antibiotics, respectively, of the 14 determined by tail flick method and hot plate latency method by us- antibiotics used. Methanolic leaf extracts of Anogeissus acuminata ing external standard indomethacin and Chitosan isolated from etha- had the maximum zone of inhibition size-29 mm against S. aureus and nol extract of Bridelia retusa. Chitosan significantly (P<0.05) showed 28 mm against E. faecalis and P. aeruginosa. Cassia tora had 29 mm the anti-inflammatory and analgesic activity in experimental animals. as the zone of inhibition size for E. faecalis, E. aerogenes, and P. Therefore the present study justifies that the isolated flavonoid ex- aeruginosa. Based on the minimum inhibitory concentration and mini- hibits significant analgesic and anti-inflammatory activity at a dose mum bactericidal concentration values, the most effective 10 plants 9 of 250 mg/kg. against uropathogens could be arranged in decreasing order as fol- lows: C. tora > A. acuminata > Schleichera oleosa > Pterocarpus Aqueous and alcohol extract of bark of Bridelia retusa exhibited santalinus > Eugenia jambolana > Bridelia retusa > Mimusops dose dependant significant activity against carrageenan induced rat elengi > kunthianum > Tectona grandis > paw edema in the dose of 50 and 100 mg/kg, p.o.10 Petroleum ether, Anthocephalus cadamba. The following eight plants had moderate chloroform, methanol and aqueous extracts of the stem bark of Bridelia control capacity: Artocarpus heterophyllus, Azadirachta indica, airy -shawii. (Euphorbiaceae) were evaluated by using carrageenan Dalbergia latifolia, Eucalyptus citriodora, Gmelina arborea, induced rat paw edema and cotton pellet granuloma method in rat. Pongami apinnata, Pterocarpus marsupium, and Shorea robusta. The anti oxidant activity of all the extracts was determined by using E. coli, followed by A. baumannii, C. freundii, E. aerogenes, P. Nitric oxide scavenging assay. It was observed that, all the extracts significantly inhibited the carrageenan induced rat paw edema at the mirabilis, and P. aeruginosa were controlled by higher amounts/ 13 dose of 200 mg/kg b.w. orally, when compared with control and stan- levels of leaf extracts. The in vitro antimicrobial activity of the crude dard drug Ibuprofen. Extracts also suppressed the granulomatous methanolic and ethanolic leaf extract of Bridelia retusa (L.) Spreng.was tissue formation of chronic inflammation, when compared with stan- studied against four gram negative and two gram positive bacteria. dard drug Diclofenac sodium. The stem bark of B. airy – shawii The results showed that both the extracts showed antimicrobial ac- extracts showed significant free radical scavenging activity against tivity. Maximum zone of inhibition was observed in the methanolic nitric oxide (NO*) induced release of free radicals.11 extract against Escherichia coli which was 29.5 ± 0.50 mm.However,

Journal of Pharmacy Research Vol.9 Issue 7.July 2015 415-418 Ghawate V. B. et al. / Journal of Pharmacy Research 2015,9(7),415-418 ethanolic extract showed least activity against Staphylococcus aureus. allergic challenge by sheep RBCs and by neutrophil adhesion test. The basis of this plant extract in the traditional treatment of diarrhea On oral administration of the extract a significant increase neutrophil in human is highlighted.14 Bark extract of B. retusa was studied against adhesion in and delayed type hypersensitivity response whereas the 4 bacterial species viz. Staphylococcus aureus, Klebsiella pneumo- humoral response to sheep RBCs was unaffected. Thus Bridelia nia, Pseudomonas aeroginosa and Proteus vulgaris and 2 fungal retusa significantly potentiated the cellular immunity by facilitating species Candida albicans and Aspergillus niger. Acetone extract the foot pad thickness responses to the sheep RBCs in sensitized showed MIC values ranging from 25, 42.5 to 85 mg/ml against the rats. With a dose of 200 mg/kg the delayed type hypersensitivity tested strains.15 response, the responses were statistically significant when they were compared with the control. The study stated that Bridelia retusa

3. Protective role on kidney and liver after CCl4 intoxication: Protec- shows a significant stimulation of the cell mediated immunity and no tive role of bark extracts of Bridelia retusa S. was studied on the liver effect on the humoral immunity .18 and kidney after CCl4 intoxication. The bark of Bridelia retusa S. was powdered and subjected to sequential extraction based on polarity 5. Total phenolic content and antioxidant activity: Effect of influence using solvents such as petroleum ether, chloroform, ethanol and dis- of solvents (possessing different dielectric constant values) and geo- tilled water. The extract was filtered, concentrated, dried and stored in graphical location on the Total Phenolic Content (TPC) and antioxi- refrigerator until further use. Oral suspensions containing 25 and 50 dant activity of extracts of Bridelia retusa bark was studied. The bark mg/kg body weight of ethanolic and aqueous extracts were adminis- was collected from two different geographical locations of India tered for 5 days to carbon tetrachloride treated female mice. The pro- [Maharashtra (MAH) and Andhra Pradesh (AP)]. The highest extrac- tective role of ethanolic and aqueous stem bark extracts of Bridelia tive values were found to be as 20.70±0.56 %w/w and 18.43 ± 0.97 retusa S. were investigated on histological profiles of liver and kid- %w/w in case of methanolic extracts of Bridelia retusa bark collected ney. The effect of 50 mg of ethanolic extract was visible by reduced from MAH and AP regions respectively while the total polyphenolic

CCl4 induced toxicity on the histology of liver and kidney which were contents in the methanolic extract of Bridelia retusa bark were 32.52 restored to that of normal better than aqueous extract wherein steato- ± 0.24 mg/100 gm and 28.04±0.67 mg/100gm in MAH and AP regions sis and dilation of central vein caused by CCl4 was reduced and respectively. The methanolic extract of the species from MAH exhib- normalized hepatocytes. Hence, the present study indicates that both ited the highest radical scavenging activity while that from AP showed the extracts possessed amelioration of histological changes in the less scavenging activity. The extracts showed a positive correlation liver and kidney of CCl4 intoxicated mice though ethanolic extract between the polyphenol contents and solvent’s dielectric constant showed better recovery in dose dependent manner. 16 (R=0.728, P<0.05). This suggests that dielectric constant value sig- nificantly influences the choice of solvent for extraction as well as the Oral suspensions containing 25 and 50 mg/kg body weight of ethanolic total phenolic contents and subsequently the antioxidant activity of and aqueous extracts of bark of Bridelia retusa S. were administered the plant extract.19 for 5 days to carbon tertrachloride treated female mice. The protective role of ethanolic and aqueous stem bark extracts of Bridelia retusa S. 6. Hypoglycemic effect: Bridelia retusa bark was screened for hy- were investigated on histological profiles of liver and kidney. The poglycemic effect on alloxan induced rats. Albino rats were divided effect of 50 mg of ethanolic extract was visible by reduced CCl4 in- into groups received different treatments consisting of control, duced toxicity on the histology of liver and kidney which were re- methanolic, pet-ether and n-butanol extracts (200 and 400 mg/kg) and stored to that of normal better than aqueous extract. It was observed standard drug Glibenclamide (5 mg/kg, p.o.) blood glucose level was that both the extracts possessed ameriolation of histological changes estimated using GOD/POD method. Results showed that Bridelia in the liver and kidney of CCl4 intoxicated mice though ethanolic retusa extracts does not affected blood glucose in normal rats but in extract showed better recovery in dose dependent manner.17 alloxan induced diabetic rats n-butanol extract showed significant fall of blood glucose level. Phytochemical analysis showed presence of 4.Immunomodulatory activity: Immunomodulatory effect of Bridelia steroids, triterpenoids, tannins and flavonoids as major constituents.20 retusa was studied in experimental rats. Bridelia retusa was adminis- tered orally at a dose of 200 mg/kg to healthy rats divided into three CONCLUSION: groups consisting of six animals each. The assessment of Now a days, research on Indian traditional medicinal plants has gained immunomodulatory activity was carried out by testing the humoral a new recommence. Although, the other systems of medicine are (antibody titre) and cellular (foot pad swelling) immune responses to effective they come with a number of undesired effects that often

Journal of Pharmacy Research Vol.9 Issue 7.July 2015 415-418 Ghawate V. B. et al. / Journal of Pharmacy Research 2015,9(7),415-418 lead to serious complications. Being natural, herbal medicine allevi- tivities of Bridelia retusa methanolic fruit extract in experi- ates all these problems.Bridelia retusa bark has been used tradi- mental animals.Scientific World Journal. 2014;2014: 1-12. tionally in Indian medicine for the treatment of broad spectrum of 9. Kilaru A, Pal B, Antony SA. Isolation of chitosan from disorders.The present study scientifically demonstrated the Bridelia retusa for analgesic and anti-inflammatory activi- antinociceptive and anti-inflammatory potential of fruit of B. retusa ties. Research Journal of Pharmaceutical, Biological and methanolic extract. These effects may be attributed to the presence Chemical Sciences. 2011; 2(3): 349-357. of polyphenolic phytoconstituents in the extract. While studying 10. Mehare ID, Hatapakki BC. Anti-inflammatory activity of bark the antimicrobial potentials of bark extract of B. retusa it shows of Bridelia retusa Spreng. Indian Journal of Pharmaceuti- significant activity against various pathogens. The extract was in- cal Sciences. 2003;65(4): 410-411. vestigated for nephroprotective and hepatoprotective activity. The 11. Tatiya AU,Saluja AK, Surana SJ. Evaluation of anti-oxidant present study indicates that both the extracts possessed ameliora- and anti-inflammatory activity of stem bark of Bridelia airy tion of histological changes in the liver and kidney of CCl4 intoxi- –shawii in rats. Journal of natural remedies.2008; 8(1): 18- cated mice though ethanolic extract showed better recovery in dose 23. dependent manner. While studying the immunomodulatory activity 12. Jadhav N,Kulkarni S,Mane A,Kulkarni R,Palshetker A,Singh it is observed that Bridelia retusa significantly potentiated the cel- K,Joshi S,Risbud A,Kulkarni S. Antimicrobial activity of plant lular immunity by facilitating the foot pad thickness responses to extracts against sexually transmitted pathogens.Nat Prod the sheep RBCs in sensitized rats. The total polyphenolic contents Res. 2014;27:1-5. in the methanolic extract of Bridelia retusa bark were 32.52 ± 0.24 13. Mishra MP,Padhy RN. In Vitro antibacterial efficacy of 21 mg/100 gm which wass responsible for significant antioxidant activ- Indian timber-yielding plants against multidrug-resistant ity. During study of hypoglycemic activity results showed that bacteria causing urinary tract infection. Osong Public Health Bridelia retusa extracts does not affected blood glucose in normal Res Perspect. 2013;4(6):347-57. rats but in alloxan induced diabetic rats n-butanol extract showed 14. Khan NA, Khan AA. Antimicrobial activities of Bridelia significant fall of blood glucose level. All the above mentioned retusa (L.) Spreng. belonging to family Euphorbiaceae. 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