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Current Trends in Biotechnology and Pharmacy Vol. 10 (2) 186-193 April 2016, ISSN 0973-8916 (Print), 2230-7303 (Online) 186 Abstract Cordia dichotoma is a tall tree which grows in Sri Lanka, India and other warmer countries. Its medicinal properties are known since long time and it is traditionally used to cure several ailments. Its fruits are used as expectorant, astringent, coolant, emollient, purgative and anthelmintic. Anti-inflammatory, analgesic, hepatoprotective and several other pharmacological activities have also been reported from the plant. Aim of the current review was focused on the assessment of its present medicinal uses, phytochemistry and pharmacology in order to reveal its complete pharmacological and therapeutic potentials. Literature survey performed on electronic sources, scientific journals as well as books showed that this plant is of an enormous value because of its various potent pharmacological actions shown by it and several pharmacologically active principles like apigenin, arabinoglucan, quercetin which have been isolated from it. It will be certainly valuable to explore it for further research to be carried out on this medicinal plant. Keywords - Cordia dichotoma, Pharmacology, Phytochemistry, Traditional uses Introduction Cordia dichotoma belonging to family Boraginaceae is a 3-4 m tall tree with 2-5 cm long petiole, 6-13×4-9 cm leaf blade ovate to elliptic, sparsely pubescent or glabrous, margin usually subundulate to undulate dentate which grows in Sri Lanka, India and other warmer countries (Fig. 1) (1). It is commonly known as Indian cherry in English and Lasora in Hindi. Its medicinal properties is known since long time and traditionally used to cure several ailments. Its fruits are used as expectorant, astringent, coolant, emollient, purgative and anthelmintic (2). Anti-inflammatory, analgesic, anticancer, hepatoprotective and several other pharmacological activities have also been reported from the plant (3, 4, 5). ‘Instant Joshanda Granules’, a polyherbal formulation, is extensively used by the people of India for the treatment of cough, sore throat, catarrh, common cold, respiratory distress, flu-like ailments and fevers of which Cordia dichotoma is the chief ingredient (6). Traditional uses : Leaf paste of Cordia dichotoma Forst is given to the animal with water for the treatment of diarrhea in Udaipur district of Rajasthan. Leaves and fruits of the plant Cordia dichotoma are given to the animals suffering from leucorrhoea (7). The fruit of the plant is used as purgative, diuretic, antihelmintic and is useful in dry cough, wound purification, mouth ulcer cure and jaundice cure and to increase male potency (8, 9). Leaves of the plant are used for headaches and ulcers including decoction for sore throat (10). The bark of the plant is used in the treatment of ulcerative colitis Phytochemistry and pharmacology of traditionally used medicinal plant Cordia dichotoma Linn (Boraginaceae) Md. Azizur Rahman 1 * and Juber Akhtar 2 1 Bioactive Research Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh (INDIA)- 226026 2 Department of Pharmaceutics, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh (INDIA)- 226026. *For correspondence - [email protected] Phytochemistry and pharmacology of traditionally used medicinal plant Cordia dichotoma Linn

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Current Trends in Biotechnology and PharmacyVol. 10 (2) 186-193 April 2016, ISSN 0973-8916 (Print), 2230-7303 (Online)

186

AbstractCordia dichotoma is a tall tree which

grows in Sri Lanka, India and other warmercountries. Its medicinal properties are knownsince long time and it is traditionally used to cureseveral ailments. Its fruits are used asexpectorant, astringent, coolant, emollient,purgative and anthelmintic. Anti-inflammatory,analgesic, hepatoprotective and several otherpharmacological activities have also beenreported from the plant. Aim of the current reviewwas focused on the assessment of its presentmedicinal uses, phytochemistry andpharmacology in order to reveal its completepharmacological and therapeutic potentials.Literature survey performed on electronicsources, scientific journals as well as booksshowed that this plant is of an enormous valuebecause of its various potent pharmacologicalactions shown by it and severalpharmacologically active principles like apigenin,arabinoglucan, quercetin which have beenisolated from it. It will be certainly valuable toexplore it for further research to be carried outon this medicinal plant.

Keywords - Cordia dichotoma, Pharmacology,Phytochemistry, Traditional uses

IntroductionCordia dichotoma belonging to family

Boraginaceae is a 3-4 m tall tree with 2-5 cmlong petiole, 6-13×4-9 cm leaf blade ovate to

elliptic, sparsely pubescent or glabrous, marginusually subundulate to undulate dentate whichgrows in Sri Lanka, India and other warmercountries (Fig. 1) (1). It is commonly known asIndian cherry in English and Lasora in Hindi. Itsmedicinal properties is known since long timeand traditionally used to cure several ailments.Its fruits are used as expectorant, astringent,coolant, emollient, purgative and anthelmintic (2).Anti-inflammatory, analgesic, anticancer,hepatoprotective and several otherpharmacological activities have also beenreported from the plant (3, 4, 5). ‘InstantJoshanda Granules’, a polyherbal formulation,is extensively used by the people of India for thetreatment of cough, sore throat, catarrh, commoncold, respiratory distress, flu-like ailments andfevers of which Cordia dichotoma is the chiefingredient (6).

Traditional uses: Leaf paste of Cordiadichotoma Forst is given to the animal with waterfor the treatment of diarrhea in Udaipur districtof Rajasthan. Leaves and fruits of the plantCordia dichotoma are given to the animalssuffering from leucorrhoea (7). The fruit of theplant is used as purgative, diuretic, antihelminticand is useful in dry cough, wound purification,mouth ulcer cure and jaundice cure and toincrease male potency (8, 9). Leaves of the plantare used for headaches and ulcers includingdecoction for sore throat (10). The bark of theplant is used in the treatment of ulcerative colitis

Phytochemistry and pharmacology of traditionally usedmedicinal plant Cordia dichotoma Linn (Boraginaceae)

Md. Azizur Rahman1* and Juber Akhtar2

1 Bioactive Research Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy,Integral University, Lucknow, Uttar Pradesh (INDIA)- 226026

2 Department of Pharmaceutics, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh(INDIA)- 226026.

*For correspondence - [email protected]

Phytochemistry and pharmacology of traditionally used medicinal plant Cordia dichotoma Linn

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187

and colic pain (8). 100 g powder of stem bark istaken with a glass of water to cure menstrualdisorders by Korku tribe of Amravati district ofMaharashtra, India (11). It is used as abortifacientin traditional or folkloric medicine (12). Thepickled fruit is eaten as an appetizer in certainareas of Taiwan. The indigestible seeds andsticky pulp of the fruit can form a phytobezoar ifingested excessively (13).

Phytochemistry: The dry powdered seeds ofCordia dichotoma were found to containglycosides, alkaloids, carbohydrates, tannins andsaponins (14). Alkaloids, flavonoids, amino acidsand proteins are present in the fruits of Cordiadichotoma (8, 9). Qualitative phytochemical tests,thin layer chromatography and TLC-bioautography of the ethanolic extract of leavesdemonstrated the presence of commonphytoconstituents phenols, tannins andglycosides as major active constituents (15, 16).The antinutritional factors such as phytic acid(0.2±0.1%), tannin (1.386±0.0152%) and oxalicacid (2.133±0.2081%) were found to be presentin the powdered wild edible fruits of the plant.Saponin was absent (17). Cordia dichotoma Forstbark was identified as botanical source ofShleshmataka in Ayurvedic pharmacopoeia (18).Apigenin was isolated by columnchromatography from methanolic fraction ofcrude methanolic extract of C. dichotoma bark

(19). Arabinoglucan was isolated from the fruitsof Cordia dichotoma Forst (20). Thephytoconstituents arabinoglucan, D-glucose andL-arabinose were present in fruits; linolenic acidin seed; and quercetin in leaves (21). Thestructure and properties of the newly identifiednatural cellulose fabrics from the branches of theCordia dichotoma indicated that they could beappropriate for blending and processing bybiodegradable polymers to make greencomposites (22).

Pharmacological activitiesAnalgesic, antibacterial and cytotoxicactivities: The crude ethanol extract of theleaves of Cordia dichotoma produced significantwrithing inhibition in acetic acid induced writhingin mice at the oral dose of 500 mg/kg b wt(p<0.001) which was comparable to that of thestandard drug diclofenac sodium at the dose of25 mg/kg b wt. The extract showed significantzone of inhibition against both Gram negative andGram positive bacteria Streptococcus aureus,Streptococcus pyogenes, Vibrio cholerae,Streptococcus epidermis, Hafnia and Escherichiacoli in disc diffusion study which is comparableto that of Kanamycin (30 ìg/ml). The extract alsoshowed potent toxicity against the brine shrimpArtemia salina (LC

50: 20 ìg/ml and LC

90: 180 ìg/

ml) in brine shrimp lethality bioassay (3).

Fig. 1. Parts of Cordia dichotoma. (A) Whole plant; (B) twig with leaves and fruits; and (C) twig with flowers.

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Anthelmintic activity: Five concentrations (10,25, 50, 75 and 100 mg/ml) of ethanolic andaqueous extracts prepared from pulp obtainedafter separation of seeds from fruits of Cordiadichotoma Forst by Soxhlet extraction werestudied for anthelmintic activity by using Eudriluseuginiae earthworms. Both ethanolic andaqueous extracts showed paralysis and death ofworms in concentration dependent manner.Aqueous extract showed significant activity thanethanolic extract. The extracts also showed thepresence of alkaloid, glycoside, saponin,flavonoid, triterpenoid, protein, amino acid andcarbohydrate in preliminary phytochemicalinvestigation (2).

Antibacterial activity: Antibacterial activity ofalcoholic and aqueous extracts of thirty fourmedicinal plants including Cordia dichotoma werescreened for potential antibacterial activityagainst six bacterial strains belonging toEnterobacteriaceae, viz., Escherichia coli,Enterobacter aerogenes, Klebsiella pneumoniae,Salmonella typhimurium, Proteus mirabilis andProteus vulgaris by the agar well diffusion anddisc diffusion methods. The ethanol extracts weremore active than aqueous extracts for all theplants studied. Aqueous extract of Cordiadichotoma inhibited only to Proteus mirabilis,while ethanolic extract inhibited to Klebsiellapneumonia and Proteus mirabilis (23).

Antibacterial activity of Cordia dichotomaleaves extract studied by two different methodsi.e. well diffusion and disc diffusion methodsagainst the strain of E. coli revealed that itpossesses antibacterial activity against E. coli.The activity of extract is due to the flavonoidactive constituent. Phytochemical analysisshowed positive result for tannin, protein andflavonoid (24).

Antibacterial activity of petroleum ether,chloroform, methanol and aqueous extracts ofCordia dichotoma Forst ripened fruits againsturinary tract pathogens such as Pseudomonasaeruginosa, Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Proteus vulgaris

and Staphylococcus aureus using disc diffusionmethod was evaluated. Results of the studyshowed that the methanolic extract exhibitedbetter antibacterial activity against the bacterialstrains as compared to other extracts (25).

Antioxidant activity or free radical scavengingactivit: The methanolic extract of seeds andleaves of Cordia dichotoma demonstratedpositive antioxidant activity in a concentrationdependent manner during investigation of theirfree radical scavenging potential using in vitromodels viz., 1,1-diphenyl-2-picrylhydrazyl(DPPH) and hydrogen peroxide (H

2O

2) models.

The IC50

values for the leaves were found to be51.83 ìg/ml and 55.73 ìg/ml for DPPH and H

2O

2

models respectively. The IC50

values for seedswere found to be 57.22 ìg/ml and 48.28 ìg/ml forDPPH and H

2O

2 models respectively. In both the

models, the methanolic extract of the leavesexhibited low IC

50 values as compared to the

seed’s extracts. Thus, this activity was morepronounced in leaves as compared to seeds (26).

During nitroblue tetrazolium chloride (NBT)superoxide radical scavenging assay, maximumantioxidant activity of ethanol and acetoneextracts of the fruits of the plant Cordia dichotomawas noticed to be 54.5 and 55.5 % respectively.The inhibitory potential expressed in IC

50 values

of acetone and ethanol extracts of C. dichotomawere found to be 131.0 and 149.0 ìg/mlrespectively (27).

The activity of peroxidase (POX),superoxide dismutase (SOD) and catalase (CAT)was determined in the fruits. The SOD and CATactivities were increased in mature fruits thanripened fruits, whereas POX activity was foundto be more in ripened fruits as compared tomature fruits (28).

C. dichotoma contains a considerableamount of phenols. The IC

50 value was found to

be 28 µg/ml for the methanolic extract and 36for butanolic extract in DPPH scavenging assay.The study revealed that the bark has significantradical scavenging activity (18).

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Antidiabetic activity: Marles and Farnsworthprovided information on more than 1200 speciesof plants reported to have been used to treatdiabetes and/or investigated for antidiabeticactivity, with a detailed review of representativeplants and some of great diversity of plantconstituents with hypoglycemic activity (29). Theaerial parts of Cordia dichotoma administeredorally were devoid of normal antidiabetic activity.

The dose of 500 and 1000 mg/kg b. wt. ofaqueous extract of the leaves administered orallyto alloxan induced and normoglycemic Wistarrats showed a significant (p<0.5) decrease inblood glucose levels after 4, 8 and 24 h. The doseof 1000 mg/kg b. wt. of the extract innormoglycemic rats significantly (p<0.05)decreased the blood glucose levels at 8 and 24h (30).

The methanolic extract of the fruits ofCordia dichotoma reduced the blood glucoselevel in glucose loaded animal and alloxaninduced diabetic animal models when comparedto diabetic control group and exerted significanthypoglycemic and antidiabetic activitiescompared to standard drug metformin. Theextract also reduced the rate of body weight lossin normal and alloxan induced diabetic animals(31).

Antimicrobial activity: Alcohol is found to be abetter solvent for extraction of antimicrobiallyactive substances compared to water andhexane (32). Ethanolic extract of the leavesshowed antimicrobial activity only against S.aureus (inhibition zone: 21-30 mm) and S.dysenteriae (inhibition zone: 10-20 mm) in thestudy antimicrobial activity against certain drug-resistant bacteria Salmonella paratyphi,Staphylococcus aureus, Escherichia coli, Bacillussubtilis, Shigella dysenteriae and a yeast Candidaalbicans of clinical origin. No correlation wasobserved between susceptibility of test strainswith the extract and antibiotic resistance behaviorof the microbial strains (15).

The acetone, chloroform, hexane, aqueousand ethanol extracts of the C. dichotoma leaves

and the chloroform, aqueous and acetoneextracts of the C. dichotoma stem bark did notshow any antimicrobial activity against testedstrains of bacteria and fungi determined bymacrobroth dilution method on the concentrationof 25 mg/ml to 0.10 mg/ml of the extracts. Onlythe hexane and ethanol extracts were activeagainst only certain fungal strains (33).

The acetone and ethanol extracts of Cordiadichotoma fruits exhibited highest antimicrobialactivity against Staphylococcus epidermidis,Staphylococcus aureus, Escherichia coli,Candida albicans and Aspergillus niger. Acetoneextract showed maximum inhibitory zone of 19.1mm whereas no inhibitory effect was observedfor the aqueous extract (27).

Petroleum ether, benzene, chloroform,acetone, methanol and aqueous extracts of theplant were investigated for the antimicrobialefficacy by modified Kirby-Bauer disc diffusionmethod against the clinical isolates of oral cancercases like the fungal pathogens Aspergillusfumigates, Candida albicans and bacterialpathogens Escherichia coli, Staphylococcusaureus, Staphylococcus epidermidis, Klebsiellapneumonia, Pseudomonas aeruginosa, Proteusvulgaris, Proteus mirabilis. Only S. aureus wasinhibited significantly by the petroleum ether andacetone extracts (inhibition zone: 10 and 11.33mm respectively; MIC: 250 and 125 ìg/mlrespectively), while only S. epidermidis byaqueous extract (inhibition zone: 10.33 mm; MIC:125 ìg/ml). Even, other isolates were not inhibitedby the remaining extracts (34).

The methanolic and butanolic extracts ofthe bark showed remarkable zone of inhibitionof bacterial growth and fungal growth comparablewith that of standard drugs against the organismstested Escherichia coli, Pseudomonasaeruginosa, Staphylococcus pyogenes,Staphylococcus aureus, Aspergillus niger,Aspergillus clavatus, and Candida albicans. Theactivity of the extracts increased linearly withincrease in extract concentration (35).

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Antiulcer activity: Ethyl acetate, butanol andbutanone fractions of ethanolic fruit extractsignificantly decreased the volume of gastricsecretion, free acidity, total acidity and ulcer indexwith respect to control during the study of anti-ulcer effect of fruit extracts (300 mg/kg b wt) inWistar rats using pyloric ligation, aspirin andindomethacin induced ulcer models (36).

The aqueous extract of fresh ripened fruitswas found to be more effective than alcoholicextract as compared to ranitidine in aspirininduced gastric ulcer model (p<0.001) as wellas in pylorus ligation model in rats (37).

Anti-inflammatory activity: The ethanolic andaqueous extracts of Cordia dichotoma Forstseeds at a dose of 250 mg/kg and 500 mg/kgorally showed significant activity compared withthe control and diclofenac sodium (10 mg/kg asstandard) in dextran-induced paw edema andcarrageenan-induced paw edema models in ratson different phases of acute inflammation (14).

Apigenin (5 mg/kg b wt, po) showedsignificant healing and reduction in inflammatoryenzymes myeloperoxidase (MPO) (from 360±0.2U/ml due to acetic acid induction to normal222±22.5 U/ml due to treatment) andmalondialdehyde (MDA) (from 9.98±1.5 nmol/mlto 2.11±1.5 nmol/ml) when screened forulcerative colitis induced by intrarectaladministration of 150 ìl, 5% acetic acid (pH 2.5)3 cm from the anal margin. It was concluded thatapigenin from C. dichotoma bark may beresponsible for the treatment of ulcerative colitis(19).

The methanol fraction of methanolic extractof C. dichotoma bark showed effective treatmentof ulcerative colitis. It showed good healing andlower pathological scores in treated animals. Itsignificantly reduced MDA and MPO levels intissue and blood. It showed antioxidant potentialand contains a high level of phenolics (38).

Anticerebrovascular insufficiency activity:Long term cerebral hypoperfusion in rats resulted

in propensity towards listlessness and anxiety(elevated plus maze test and open fieldparadigm) accompanied by deficits in memoryand learning (Morri’s water maze test) andtendency towards depression (Porsolt’s swimtest). Gliosis, cellular edema, astrocytosis andinflammatory changes were observed inforebrain. Treatment by Cordia dichotoma (250mg/kg po for 28 days) alleviated these cognitive,behavioral and histopathological changessuggesting that Cordia dichotoma may be usefulin cerebrovascular insufficiency conditions (39).

Binding property: The mucilage isolated fromthe aqueous filtrate of macerated seeds, whosepulp was previously removed, possesses bindingproperty comparable to the starch. An increasein mucilage concentration led to decrease infriability and increase in disintegration time of thetablets (40).

Angiotensin converting enzyme inhibitoryactivity : The ethanolic extract of bark showedhigh ability to inhibit the angiotensin convertingenzyme (41).

Diuretic activity : Petroleum ether, solvent etherand butanol fractions of alcoholic extract of thefruits 300 mg/kg b wt were tested for diureticactivity in rats for total urine volume, urineconcentration of Na+ and K+ and showed increasein cation excretion and urine volume (42).

Hepatoprotective activity: The methanolicextract of the leaves (300 mg/kg) significantlyreduced the alanine aminotransferase (ALT)(p<0.001), aspartate aminotransferase (AST)(p<0.001) and thiobarbituric acid reactivesubstances (TBARS) levels (p<0.01); and at 500mg/kg extract dose significantly reduced the AST(p<0.001), ALT (p<0.001), TBARS (p<0.01) andlipid peroxide levels (p<0.05) in male Wistar ratswith liver damage by carbon tetrachloridetreatment (4).

Antifertility activity: The reversible nature of thedeveloped phytopharmaceutical was studied byperforming pharmacological analyses followedby chronic toxicity studies. The biochemical and

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histological estimations detected the reversiblecontraceptive potential of the drug afterwithdrawal. The observations also suggested thatthe developed phytopharmaceutical had potentialantifertility activity with safety aspects (43).

Wound healing activity: Petroleum ether,solvent ether, ethyl acetate, butanol and butanonesuccessive fractions of the ethanolic extract ofCordia dichotoma fruits showed significant(p<0.001) wound healing activity on excision,incision and dead space wound models on Wistaralbino rats (44).

ConclusionCurrent review summarizes many

important pharmacological studies,phytochemical investigations and isolatedphytoconstituents of Cordia dichotoma which canbe further assessed to find out lead moleculesin the search of novel herbal drugs for thetreatment of several diseases.

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