Review Article
ejbps, 2015, Volume 2, Issue 6, 260-265.
SJIF Impact Factor 2.062
2349-8870 Europeanof Journal of Biomedical and Pharmaceutical ISSN Sciences European Journal Biomedical Volume: 2 Issue: 6 AND Pharmaceutical sciences
Mujeeb et al.
260-265 Year: 2015
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A REVIEW ON PHARMACOLOGICAL AND TOXICOLOGICAL POTENTIALS OF CASSIA OCCIDENTALIS LINN Fakiha Firdous1, Mohd Mujeeb1*, Rohit Sharma1, Asif Hudsain2 Anwar Husain Khan3, Mohammad Akram4 1
Department of Pharmacognosy and Phytochemistry, Department of Pharmaceutical chemistry, Faculty of Pharmacy, 3 Department of Anatomy and Physiology, 4Department of Preventive and Social Medicine Faculty of Unani Medicine, Jamia Hamdard (Hamdard University), New Delhi - 110 062, India. 2
*Author for Correspondence: Mohd Mujeeb Department of Pharmacognosy and Phytochemistry, Jamia Hamdard (Hamdard University), New Delhi - 110 062, India. Article Received on 21/09/2015
Article Revised on 10/10/2015
Article Accepted on 31/10/2015
ABSTRACT Cassia occidentals L. is an important medicinal plant which grows as a weed in tropical regions of the world as a perennial plant. It has been used in various folklore medicines of tropical origin. It possesses anti-bacterial, antifungal, anti-malarial, larvicidal, anti-oxidant, anti-inflammatory and many other properties. The plant, though have medicinal properties, have been reported to cause severe toxicity and deaths have been reported in northern part of India due to consumption of seeds of C.occidentalis. The review gives a brief account of the medicinal properties that the plant holds and also discusses its toxic nature. KEYWORDS: Cassia occidentals L., anti-bacterial, anti-fungal, anti-malarial, larvicidal, anti-oxidant, antiinflammatory.
Figure 1: Cassia occidentalis Linn plant and its seeds INTRODUCTION Cassia occidentalis L. (Caesalpiniaceae) is an important medicinal plant with different medicinal properties. C. occidentalis is a weed of the humid tropics and subtropics, principally on silts and sands, becoming a weed on roadsides, in arable lands, degraded pastures and waste places. It is commonly known as Coffee senna, fetid cassia, and Negro Coffee[1].C. occidentalis L. was transferred to the genus Senna and is now also known as Senna occidentalis. It is a short growing, sparsely branched annual herb or shrub (0.5 to 2.0 m) with a characteristic fetid odour The stems are erect,
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reddish purple in appearance, four sided when young and becoming rounded with age. The leaves are pale green in colour, alternate, pinnate, with 3-5 (sometimes 6) pairs of opposite ovate to lanceolate-elliptic leaflets, 25-100 mm long, 20-30 mm wide, rounded at the base. A conspicuous, dark-coloured gland occurs at the base of the petiole (leaf stalk) but not on the stalks of the leaflets. The flowers are pale to bright yellow 2 cm long with 5 yellowish green sepals with distinct red veins and 5 yellowpetals. The fruit is a dry, dehiscent, transversely partitioned, faintly recurved, laterally compressed, sickle shaped legume (pod), 7–12 cm long, 8–10 mm wide,
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with rounded tip andcontaining 25–50 seeds. Seeds are oval shaped, 3.5–4.5 mmwide, flattened; pale to dark brown, slightly shiny, smoothand with a round pointed tip[2,3] (Figure-1). C. occidentalis has been reported to have toxic nature in several occasions but yet is consumed as ‘famine food’ and considered as ‘Edible food of agriculture[4]. The plant has many different pharmacological actions and has been used by tribals in various countries for treating various ailments since ages. The phytoconstituents in plants may vary depending upon the climatic condition, soil types and various other factors. The phytoconstituent found in leaves of C.occidentalis are chrysophanol, emodin and their glycosides, physicon, bianthraquinones. Roots of the plant mainly contain emodin, 1,8 dihydroxyanthraquinone, quercetin,emodol, physicon, chrysophanol, islandicin, questin, chrysophanol 10,10’ bianthrone, germichrysone, rhein, aloe-emodin, their glycosides, α- hydroxyanthraquinone[5-6].Seeds are found to possess phytoconstituentsemodin, aloe-emodin, rhein, chrysophanol, physicon, 1,8-dihydroxy-2methylanthraquinone, 1,4,5-trihydroxy-7-methoxy-3methylanthraquinone,1-Glucoside-3-methyl,6-methoxy1,8-dihydroxy anthraquinone. Flowers mainly contain emodin, physicon and its glycosides[5]. PHARMACOLOGICAL ACTIVITIES Anti microbial activity C. occidentalis has been tested for its anti-microbial activity and it has been reported to be active against many diseases causing pathogens. The activity of the extract may vary with the solvents used. It may also vary with the plant parts used and microbes against which they are tested. Extracts from the leaves, flowers, pods and bark of C. occidentalis were tested against different bacteria (Pseudomonas aeruginosa, B. cerus, S. aureus, Proteus mirabilis and E. coli) and fungi (Candida albicans, Aspergillus niger, A. flavus and Fusarium oxysporum). The inhibition zone of the plant extract was found to be comparable to gentamycin and ampicillin.[79] . It has been reported that the seeds of C. occidentalis possess a strong antibacterial activity against S. aureus, B. subtilis, B. proteus and Vibrio cholerae and against fungi A. flavus, A. niger and Trichophyton mentagrophytes.[10-12] A study conducted with different extracts of methanol, aqueous, benzene, petroleum ether and chloroform extract showed that methanol extract was the most potent against P. aeruginosa, K. pneumoniae, P. mirabilis, E. coli, S. aureusand S. epidermidis; aqueous extract was effective against P. vulgaris, K. pneumoniaeand P. aeruginosa; benzene and petroleum ether extracts was active against P. mirabilis and E. coli; chloroform extract was found to be very inactive against all tested strains.[13]Another research reports that the E. coli was sensitive to methanol, hexane, chloroform and aqueous extract of leaves of C. occidentalis. The leaves were collected from Kacha town in Nigeria state. Serial concentrations of 50, 60 ,70, 80, 90, 100% of methanol, hexane, chloroform and aqueous extracts were prepared. The microbial strains tested were E. coli, P. multocida, S.
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typhi, S. typhimurium, S. pyogenes, S. pneumoniae and K. pneumonia. Anti-microbial activity against E. coli was observed with all the extracts at concentration ranges of 900-1000 mg and hexane extract was the most active at concentration ranges of 500-600 mg. No activity was observed against other microbial strains[14].The leaf extracts of n-hexane and dichloromethane of C. occidentalis were tested against eleven gram-positive viz. Bacillus subtilis, Bacillus cereus, Bacillus stearothermophilus, Micrococcus luteus, Bacillus anthracis, Staphylococcus aureus, Enterococcus faecalis, E. faecalis, Clostridium sporogenes, Corynebacteriunpyogenes and B. polymyxa and four gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli and Pseudomonas flourescens.The results revealed that both the fractions exhibited a broad spectrum activity. The resistant strains were Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Enterococcus faecalis, Corynebacteriun pyogenes, Pseudomonas flourescens. The fractions were active at a concentration of 20 mg/ml[15]. Anti-malarial activity C.occidentalis has been proved to have significant antimalarial activity[16-17]. A study carried out with ethanolic, dichloromethane and lyophilized aqueous extract of root bark of C. occidentals was evaluated for its anti microbial activity against Plasmodium berghei ANKA. The administration of extracts of C.occidentlis did not cause toxicity and mortality in mice treated orally with 500 mg/kg of body weight or the same dose given twice weekly for 4 weeks. The C.occidentalis extract was found to have potential chemosuppressions of parasitemia of >60% and the ethanolic extract were more potent in chemo suppression than lyophilized aqueous extract[18]. In another report the isolated compounds from C. occidentalis have depicted significant in vitro antimalarial activity which proves its documented traditional values[19]. Anti diabetic activity In a study conducted to determine the anti hyperglycemic activities of extract of C. occidentalis in alloxan induced diabetic mice, it was found that orally administered methanolic extracts of C. occidentalis leaves at the dose of 300 mg/kg produced significant lowering activity of fasting blood glucose in 6 and 12 hour samples compared with the control. Also an increase in the dose of C. occidentalisto 450 mg/kg showed more observable hypoglycemic activity in the diabetic mice. The activity was less when compared to that of Glibenclamide.[20]In another study carried out to evaluate the anti-diabetic activity of ethanolic extract of C. occidentalis root, it was reported that ethanolic C.occidentalis root extract exhibited significant hypoglycemic activities in streptozotocin induced diabetic mice. There was improvement observed in various body and serum parameters as well as regeneration of β cells of pancreas was reported[21].
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A marked reduction in blood glucose level of normal and alloxan induced diabetic mice was observed with oral administration of aqueous extract of C. occidentalis. Petroleum ether showed its anti-diabetic activity from day 14 and chloroform extract from day 7. A considerable change in the serum lipids, serum proteins and body weight was observed in aqueous extract treated diabetic mice. Also, histopathological studies of the pancreas revealed regeneration of pancreatic cells which were necrosed by alloxan.[22]Tests performed to compare the hypoglycemic activity of butanol extract (BE) and aqueous extract (AE) in alloxan induced diabetic mice revealed that the reduction in blood glucose level by BE (95.2±7.46) is a bit more significant as compared to AE (119.6±29.03) of C. occidentalis. The group treated with BE showed reduced plasma cholesterol level at (186 ± 14.8) which was a little more significant when compared to aqueous extract which was (190± 14.81). Similarly the BE showed significant reduction of LDL levels (99.7±7.3) and AE also showed significant activity in reduction of LDL levels (111 ± 5.1). However, these extracts were unable to show any activity against HDL and triglycerides levels.[23] Anti-oxidant activity In order to determine the antioxidant activity of C.occidentalis, the ability of its extract to scavenge hydrogen peroxide was determined according to the method by Nabavi et al.; 2008a and 2008b. In the hydrogen peroxide radical scavenging method it was found that the percentage inhibition of methanolic (MSO) extract was in the range of 28.29% – 86.03%. The lowest concentration (0.0625 mg/ml) showed the highest percentage inhibition value (86.03%).There is a characteristic increase in inhibition as the concentration decreases. The ethyl acetate (ESO) and hexane(HSO) extract also gave similar observations.[24] The order of decreasing anti oxidant activity thus is α-tocopherol > MSO > ESO > HSO. Another study was carried out to investigate the antioxidant potency of C.occidentalis using different organic solvents and aqueous extract of leaves employing various established in vitro systems such as nitric oxide scavenging (NOS) activity, β-carotene–linoleic acid model system, hydroxyl radical scavenging (HRS) activity, reducing power, metal chelating activity (MCA) and superoxide radical scavenging (SRS) activity. The aqueous extract was found to be the most active against free radicals and the activity decreased in the order methanolic > chloroform> petroleum ether > benzene extracts. In order to establish relationship between antioxidant activity and total phenolic content (TPC), a correlation analysis of different anti-oxidant capacity values with the TPC at 1mg mL-1 concentration was performed. The correlation coefficient (r) and coefficients of determination (R) were measured between antioxidant capacities and TPC and the R-values obtained were mostly positive and significant at the p < 0.05 significance level, suggesting that there were
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significant and positive correlations between antioxidant activities and TPC[25]. Hepatoprotective activity Hepatoprotective activity was tested using aqueous extract of seeds of C. occidentalis. Rat liver damage was induced by paracetamol and serum glutamic pyruvic transaminase(SGPT), serum glutamic oxaloacetic transaminase(SGOT), alkaline phosphate, total bilirubin, and histopathological alterations were monitored. The results proved that aqueous extract of C.occidentalishas marked hepatoprotective activity against paracetamol induced liver damage in rats. The activity was also found to be dose dependent[26]. In another study effect of aqueous-ethanolic extract of (50% v/v) leaves of C.occidentalis was studied on rat liver damage induced by paracetamol and ethyl alcohol by monitoring serum transaminase (aspartate amino transferase and serum alanine amino transferase), alkaline posphatase, serum cholesterol, serum total lipids and histopathological alterations. A marked hepatoprotection was noted through the results[27]. Larvicidal activity The potency of ethanolic extract of C. occidentalis was tested for its larvicidal activity against the larvae of Anopheles stephensi, the LC50value was 60.69%92.21%. The smoke proved more toxic to Anopheles stephensi.Gravid female mosquitoes that were exposed to the smoke of C. occidentalis layed fewer eggs than those were not exposed[28].Another study was conducted to determine the larvicidal activity of C.occidentalis against the larvae of Culex quinquefasciatus. These larvae transmit parasites and pathogens which are responsible for deadly diseases such as filariasis, dengue, yellow fever, malaria, and Japanese encephalitis, chikungunya which are responsible for many deaths in tropical and sub-tropical regions. In this study petroleum ether and Nbutanol extract of dried plant at various concentrations was taken against the late third instar larvae of Culex quinquefasciatus by following the WHO guidelines. It was revealed that 100% mortality effect of petroleum ether and N-butanol extract of C. occidentalis was observed at 200 and 300 ppm (parts permillion)[29].Another study revealed that seed oil creates increase in mortality of Callosobruchus maculatus eggs[30].Based on numerous trials with pure compounds suggested that fatty acids (linoleic, oleic and stearic) are responsible for C. occidentalis toxicity. The oviposition of C. maculatuswas not reduced by C. occidentalis seed oil at 10 ml/kg seed. Anti-inflammatory activity As was assayed in an experiment [31], C. occidentalis revealed to have good anti-inflammatory property. Using carrageenan induced rat paw edema and cotton pellet granuloma assay it was found that C. occidentalis was maximally active at a dose of 200 mg/kg. Also lowering of lipid peroxide content, gamma-glutamyl transpeptidase and phospholipase A2 activity in the
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exudates of cotton pellet granuloma was noted which consequently reduced availability of arachidonic acid, a precursor of prostaglandin biosynthesis, and/or by stabilization of the lysosomal membrane system.Similarly in another report[32] it was seen that C.occidentalis reduced inflammation at a dose of 250 mg/kg but higher dose (500mg/kg) showed lower level of protection. The lower dose produced effect almost equal to that of 80 mg/kg of standard drug ibuprofen. Analgesic activity In a research study carried out to determine the analgesic and anti-pyretic activity of C.occidentalis , ethanol and water extracts of the leaves were screened for antinociceptive activity using acetic acid induced writhing test, hot plate test and tail immersion test in mice and also in yeast induced pyrexia method in rats. It was reported that ethanol and water extracts both possessed dose-dependent moderate analgesic activity against various pain models used. Also both the ethanolic and water extracts of C.occidentalis showed significant effect on pyrexia induced by yeast[33]. Anti-anxiety and anti-depressant activity Anti-depressant activity of C.occidentalis leaves was evaluated in rodents using ethanolic and aqueous extracts. For anti-anxiety activity testing, rats were exposed to unfamiliar aversion in different models such as elevated plus maze and actophotometer. The results show that reduced aversion fear elicits anti-anxiety activity. The anti depressant activity was tested using despair swim test and tail suspension test. The results infer that reduced immobility time elicits anti depressant activity. Also it was concluded from the results that ethanolic extract showed more activity than aqueous extract[34]. Anti-cancer activity In vitro cytotoxicity of three extracts (alcoholic, hydroalcoholic and aqueous) of C.occidentalis at concentrations of 10, 30 and 100µg/ml were evaluated against human cancer cell lines from six different tissues origin, namely colon, prostate, breast, cervix, ovary, and lung. Inhibition of growth in a dose dependent manner was observed in all cancer cell lines. It was also observed that the most active was aqueous extract followed by hydro-alcoholic extract and then alcoholic extract[35].Various researches have attributed emodin, a phytoconstituent also found in C. occidentalis, for its anti-cancer activity. It has been reported that emodin demonstrates cytotoxic effects by arresting the cell cycles and leading to apoptosis of cancer cells. The overall molecular mechanisms of emodin include cell cycle arrest, apoptosis, and the promotion of the expression of hypoxia-inducible factor 1a, glutathione Stransferase P, N-acetyltransferase, and glutathione phase I and II detoxification enzymes while inhibiting angiogenesis, invasion, migration, chemical-induced carcinogen-DNA adduct formation, HER2/neu, CKII kinase, and p34cdc2 kinase in human cancer cells[36].
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TOXICITY STUDIES There have been several instances that point out to the toxic nature of the plant C. occidentalis. High mortality have been observed in northern part of Indiaamong children and a case control study has linked it to the consumption of seeds of C.occidentalis[37].In southern Brazil 16 outbreaks of animal death blamed to C.occidentalis. The gross changes noticed in poisoned cattles were degenerative myopathy in skeletal muscles of the hind limbs. Other organs affected were the heart, liver, kidney, and the spleen as myocardial, hepatic, renal, and splenic microscopic lesions were observed occasionally[38]. In a research study carried out to investigate the toxicity of C.occidentalis seeds (0.5%, 1% & 2%) in diets of wistar rats and the findings link C.occidentalis seed consumption as the main etiological factor in children population suffering from hepatomyoencephalopathyin India. After 28 days of administration of C.occidentalis seeds significant changes in the serum markers were observed viz transaminases, alkaline phosphatase and lactate dehydrogenase along with histopathological lesions in hepatic tissue. Decrease in grip strength, vacuolization and myopathy of skeletal muscles along with increases in serum creatinine and creatinine phosphokinase was observed which indicate muscular damage in animals. Neuronal damage was evident by a marked increase in glial fibrilar acidic protein and decrease in β-tubulin III. The findings indicate liver, muscles and heart to be the target organs which were similar to the poisoning cases caused by consumption of C.occidentalis seeds[39]. A sub-chronic toxicity study of seeds of C.occidentalis and its beverage was carried out on male and female albino mice. The test included both raw and roasted seeds of C.occidentalis. The results showed that raw seeds are toxic and its manifestation was observed by body weight loss, decrease in serum proteins level and increase in serum ammonialevel, liver enzymes (GOT and GPT) activities and Hepato-Somatic Index. The roasting of seeds at 200oC for 10 minutes rendered the seeds intoxic[40]. A pre-clinical study was carried out to study acute and sub-acute toxicity of stems and leaves of hydroalcoholic extract of C.occidentalis on male and female wistar rats. No hazardous symptoms or death was noticed in the test animals in acute toxicity test. Also there were no changes in the macroscopical and microscopical aspects of organs in animals treated with extracts of stems and leaves of C.occidentalis[41]. In an experiment carried out to investigate the effects of oral sub-acute administration of C.occidentalis during pregnancy in female Wistar rats, three groups of pregnant rats were treated orally from the 1st to the 6th day (pre-implantation period) and from the 7th to the 14th day (organogenic period) of pregnancy, with doses of 250 and 500 mg/kg. On the 20th day of pregnancy, the
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animals were euthanized and reproductive parameters were evaluated. The results revealed no statistically significant differences between the control and treated groups in terms of offspring/dam relationship; fetuses, placentae and ovaries weights; number of implantation and resorption sites; number of corpora lutea in the ovaries and pre- and post-implantation loss rates. However, the presence of dead fetuses was registered in both doses of 250 and 500 mg/kg of C. occidentalis[42]. In another experiment rabbits were used to study the biochemical aspects of intoxication of coffee senna. Intoxication of C.occidentalis in rabbits result in more severe cardiomyopathy and less skeletal muscle damage when compared to that of cattle.The ground endosperm of the seeds of C.occidentalis administered to rabbits, orally, 0.25-3.0% body weight, produced a fatal cardiomyopathycharacterized by mitochondrial degeneration, lipid accumulation, myofibrillar degeneration, myocytolysis and relatively minor reparative changes[43].The microscopic appearances of coffee senna poisoning in rabbits and cobalt toxicity in the rat are similar[44].
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12. CONCLUSION Cassia occidentalis has been used traditionally in the treatment of several ailments and the many researches carried out have also proved the plant to have extensive biological potential. The plant with such varied potential could be used for manufacturing effective medicines but before incorporating the use of such plants that show toxicity in some form its important to detoxify them and make them safe for administration. From the researches carried out to determine the toxicity of C. occidentalis is evident that the toxicity of the plant mainly lies in the seeds and the other parts of the plant are relatively safe. Raw seeds or dried seeds are poisonous but roasted seeds upto 200oC is considered safe and is used as a substitute for coffee in many places. REFERENCES 1. Parsons WT, Cuthbertson EG, Noxious Weeds of Australia. Melbourne, Australia: In kata Press, 1992; 692. 2. Roy L, Holm G, Doll J, Holm E, Pancho J, Herberger J. World Weeds: Natural Histories and Distribution Cassia occidentalis L. and Cassia tora L. (Syn. C. obustifolia L.). New York: John Wiley & Sons; 1997; 1129. 3. Long RW, Lakela O. A Flora of Tropical Florida. Miami, FL: Banyon Books; 1976; 962. 4. Humphry C, Clegg MS, Keen C, Grivetti LE. Food diversity & drought survival — the Hausa example. Int J Food Sci Nutr 1993; 44: 1–16. 5. The Wealth of India, A Dictionary of Indian Raw Materials and Industrial Products-Raw Materials, Revised Ser, Vol. 3 (Ca-Ci), Publications and Information Directorate, CSIR, New Delhi, 1992; 327-331.
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