Medical Journal of Dr. D.Y. Patil Vidyapeeth

REVIEW ARTICLE
Year
: 2016  |  Volume : 9  |  Issue : 5  |  Page : 560--565

Ethno medicinal values of Citrus genus: A review


Swapnil Y Chaudhari, Galib Ruknuddin, Pradeepkumar Prajapati 
 Department of Rasashastra and Bhaishajya Kalpana, I. P. G. T. and R. A., Gujarat Ayurved University, Jamnagar, Gujarat, India

Correspondence Address:
Swapnil Y Chaudhari
Department of Rasashastra and Bhaishajya Kalpana, I. P. G. T. and R. A., Gujarat Ayurved University, Jamnagar - 361 008, Gujarat
India

Abstract

Fruits of Citrus genus play an important role as a dietary supplement and therapeutic assent as well since ages. The present review summarizes some such attributes of Citrus genus. Literature review was done through published works to gather information on nutritional and ethnic values, phytochemical and pharmacological properties of Citrus. Information about the plant and phytochemical constituents, pharmacological activities were collected from the published reports. The plant was found to possess significant analgesic, anti-inflammatory, antioxidant, anthelmintic, antibacterial, antifungal, and hypolipidemic properties. They are found to be significant antihyperglycemic, antidiabetic, and hypoglycemic activity. The phytoconstituents which are present in the plant are mainly coumarins and flavonoids which are responsible for the actions. The phytochemical constituents and isolated bioactive compounds of Citrus can be investigated further to develop novel herbal drugs by using reverse pharmacological approaches especially in the treatment of liver diseases, arthritis, malignancies, and other inflammatory diseases.



How to cite this article:
Chaudhari SY, Ruknuddin G, Prajapati P. Ethno medicinal values of Citrus genus: A review.Med J DY Patil Univ 2016;9:560-565


How to cite this URL:
Chaudhari SY, Ruknuddin G, Prajapati P. Ethno medicinal values of Citrus genus: A review. Med J DY Patil Univ [serial online] 2016 [cited 2024 Mar 29 ];9:560-565
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Full Text



 Introduction



Despite availability of sophisticated, innovative developments of technology and modern medicine, traditional practices are still having prime importance for treating various diseases worldwide including India. The number of people using traditional medicines is rapidly increasing because of many reasons. Traditional systems of medicine such as Ayurveda, Homeopathy, etc., are gaining popularity and interest throughout the globe due to their approaches in preventive and therapeutic measures. Traditional practices use substances that available naturally in the surroundings. Most of such substances possess dietary values besides holding therapeutic values. Epidemiological evidence suggest that dietary factors play an important role in human health and in the treatment of certain chronic diseases including cardiovascular diseases, hyperlipidemia, etc.[1],[2] Citrus genus (Rutaceae) contains 130 genera in the seven subfamilies with many important fruits and essential oil producers.[3] Fruits of this genus are promising source of Vitamin C, carotenoids, coumarins, folate, and flavonoids. They are considered as important part of diet. Vitamin C is reported as an antiscorbutic and possesses antioxidant properties. Citrus flavonoids have hydroxyl radical scavenging activity and antilipoperoxidant activity.[4],[5],[6] Many pharmacological studies have been conducted to investigate the properties of Citrus in an attempt to authenticate its use as a multipurpose medicinal agent. Few review works reported on phytochemical, pharmacological actions, and health benefits of Citrus and its active components, especially in cancer.[7],[8] This review is the first attempt toward providing published research data at one place.

 Botanical Description



The plants are shrubs or trees usually spinous with alternate, 1-foliolate leaves, and coriaceous persistent. Petioles are often winged, and flowers are axillary, solitary fascicled, white or pinkish, and sweet scented. Petals are linear, oblong, thick, imbricate, and 4-8 in number. Berry is large, oblong or globose, flesh many celled, septa membranous, cells few seeded, and filled with horizontal fusiform cells distended with juice. Seeds are horizontal or pendulous, testa coriaceous or membranous, embryo sometimes two or more in one seed, cotyledons plano-convex, often unequal, radicle small, and superior.[9] Citrus trees are evergreen trees that produce fruits of different forms and sizes (from round to oblong), which are full of fragrance, flavor, and juice. They have a rough, robust, and bright color from green to yellow skin or rind known as epicarp or flavedo which covers the fruits and protects from damages. The glands contain the essential oils that give the fruit its characteristic Citrus fragrance. It consists of a white, thick, and spongy mesocarp or albedo which together with the epicarp forms the pericarp or peel of the fruit. The internal part constitutes the pulp which is divided into separate segments or juice sacs (with or without seeds, according to varieties) by a thick radical film or endocarp. This part is rich in soluble sugars, ascorbic acid, pectin, fibers, different organic acids, and potassium salt that give the fruit its characteristic citrine flavor. The exact origin of Citrus fruits is not clearly identified, although most researchers place its origin to be South East Asia.[10],[11],[12]

 Nutritional Values



Citrus fruits are commonly used as food ingredient due to the high source of nutrition value. Their protective effect may be associated mainly with the antioxidant activities of bioactive components present in it. The responsible bioactive components are Vitamin C, beta-carotene, flavonoids, limonoids, folic acid, and dietary fiber. A high intake of Citrus fruits may reduce the risk of degenerative diseases.[13] The fruits of Clonorchis sinensis, Citrus limonum, and Citrus aurantifolia showed the presence of phenols, flavonoids, reducing sugars, steroids, terpinedes, and tannins.[14]C. limonum contained more carbohydrate and calcium contents. Calcium content was as high as 80 mg/100 g in Citrus medica and in other Citrus fruits, it varied between 23.56 and 33.16 mg/100 g. Iron content is the highest in Citrus aurantium and the lowest in Citrus jambhiri. The free phenols and tannins were less in C. jambhiri and C. medica as compared to other Citrus fruits. Total free phenol content is the highest in C. medica (3.74 mg) followed by C. aurantium (2.81 mg/10 g).[15]

 Ethnic Values



C. limon (L.), Burmese fruit, is used as toothpowder to maintain orodental health.[16]C. medica, Salib fruits and leaves are used in anorexia, asthma, cancer, constipation, diarrhea, dysentery, dysmenorrhea, fever, halitosis, headaches, hemorrhoids, intestinal disorders, jaundice, piles, pulmonary, skin diseases, tumors, vomiting, worm infestations, etc.[17]C. aurantium is used in herbal medicine as a stimulant and appetite suppressant. It has also been used in traditional Chinese medicine to treat indigestion, nausea, cancer, constipation, and cardiovascular diseases.[18]

 Therapeutic Attributes in Ayurveda



Different varieties of Citrus are used in Ayurvedic pharmaceutics and therapeutics. C. medica Linn. (Bijapur) is used as appetizer, cardio-stimulant, and antiemetic. C. Jambhiri is used as antidiarrheal, improves digestion. In Rasashastra (Ayurvedic pharmaceutics), these varieties are useful in purification, incineration, and levigation procedures essential for preparation of different Ayurvedic formulations.

 Pharmacological Actions



Anti-oxidant activity

Essential oil of C. limon has shown antioxidant action in preventing lipoperoxidation and exerts an antinociceptive effect by the central inhibitory mechanisms due to changes in motor coordination in naloxone treated Swiss albino mice.[19] It also possesses significant protective action against oxidative stress in mice hippocampus during neurodegenerative diseases.[20] Continuous application of lemon essential oil solubilized in grape seed oil might be useful in the prevention of lifestyle-related skin diseases by regulating the balance of oxidative stress.[21]

Antiulcer activity

Lemon juice produced marginal ulcer healing effect and augmented the effect of pantoprazole and ranitidine in acetic acid induced chronic gastric ulcers. The juice in pyloric ligated rats demonstrated the antisecretory and antiulcer effect. Both doses of lemon juice showed the significant antiulcer effect in ethanol induced, stress induced, and indomethacin induced gastric ulcers. Lemon juice also reduced ulcer area in cysteamine induced duodenal ulcer. Co-administration of lemon juice with ranitidine or pantoprazole augments their antiulcer effect.[22] The essential oil of Citrus lemon L. (250 mg/kg) and limonene (177 mg/kg) showed marked protection of gastric mucosa in the ethanol-induced lesion model.[23]

Anthelmintic and insecticidal activity

C. sinensis and Citrus reticulate were comparatively tested as a larvicide against Aedes albopictus. C. sinensis was found to be best in terms of limonin content (LC50) (297 ppm), percentage of mortality (97%), and lethal time (LT50) (18.49 h) then C. reticulate with LC50(377.4 ppm), percentage of mortality (88%), and LT50 (31 h).[24] Fresh undiluted fruit juice of C. aurantium was found to possess promising anthelmintic activity in comparison to fresh diluted fruit juice against the Indian earthworms Pheritima posthuma.[25] Leaves of C. medica are reported to have potential to paralyze and kill earthworm (P. posthuma). The shortest time of paralysis and time of death was observed at higher dose (80 mg/ml) of petroleum ether extract was found to 30.86 min.[26]C. aurantium flavedo contains secondary metabolites with insecticidal activity against Bactrocera oleae (Gmelin) adults.[27]

Anticancer and cytotoxic activity

Intraperitoneal administration of methanolic extract of Citrus limetta fruit peel at the doses of 200 and 400 mg/kg against Ehrlich ascites carcinoma bearing Swiss mice for 9 days demonstrated a significant decrease in tumor volume, viable tumor cell count, tumor weight, and a significant improvement in hematological parameters, white blood cell count, and life span.[28]C. aurantifolia oil showed 78% inhibition of human colon cancer cells (SW-480) with 100 μg/ml concentration at 48 h. It has potential benefits in colon cancer prevention by apoptosis induction.[29]C. limon essential oil has a cytotoxic effect on the cancer cell line LIM1856 in vitro.[30] Aqueous extract of C. aurantifolia possesses cytoprotective action against aflatoxin B1 induced liver injury in rats. It significantly protected nucleic acid levels and inhibited DNA fragmentation showing ameliorative effect.[31]

Antimicrobial action

Fruit juice of C. limon inhibited clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae.[32] Peel extracts of C. sinensis has marked antibacterial action while C. aurantium revealed higher antifungal activity against Colletotrichum capsici in comparison with each other.[33] Aqueous extracts of peel and juice from fresh and dried Citrus and sweet lemon reported antimicrobial action against six Gram-positive and eight Gram-negative bacterial and one yeast isolates.[34]C. sinensis seed oil is highly effective as an antifungal agent against Lentinus sajor-caju, which caused white rot in wood hence, it can be used as a preservative agent in the management of wood infected with white rot fungi.[35]Propionibacterium acnes, bacterial species that causes Acne vulgaris is reported very sensitive to C. limon.[36] Methanolic extract of C. sinensis fruit peel was able to inhibit all the bacteria (Bacillus subtilis, S. aureus, E. coli) and fungi (Candida. albicans and Aspergillus niger) with different degrees of inhibition.[37] The high biological potential of essential oil of C. limon, against multidrug resistant Acinetobacter spp. was reported.[38]

Anti-inflammatory and analgesic action

C. medica L. peel extract is reported to have significant potential in carrageenan induced inflammatory pain in rats.[39] Limonin isolated from Citrus latifolia Tanaka. Essential oil had anti-migratory activity by inhibiting proinflammatory mediators present in the inflammatory exudate. Methanolic extract of C. limon L. fruit rind produced significant inhibition of paw edema.[40] Ethyl acetate peel extract of Citrus decumana at the dose of 300 mg/kg produced a significant decrease in paw volume and pain when compared to diclofenac and morphine.[41] Analgesic action of C. medica Linn. decoction at 1, 2, and 4 ml/kg p.o. was evaluated using tail immersion method and hot plate method against diclofenac sodium (10 mg/kg i.p.). The decoction at doses (2 and 4 ml/kg) showed a significant increase in latency to flick as compared to control in tail immersion method. It showed a significant increase in the mean basal reaction time in hot plate method at all three doses. In both the methods, the analgesic effect of 4 ml/kg decoction was observed comparable to the standard drug.[42]

Hepatoprotective action

Citrus microcarpa peel extract showed hepatoprotective activity against acetaminophen-induced liver damage in male Sprague–Dawley rats. A significant decrease in serum enzyme levels and lack of any gross morphological injury to the rat's liver was observed.[43] The ethanolic extract of C. limon L. fruit was evaluated for its effects on experimental liver damage induced by carbon tetrachloride. It normalized the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin, which were altered due to carbon tetrachloride intoxication in rats.[44]

Estrogenic activity

Significantly decrease sperm count was found after administration of alcoholic extract and its fractions of C. limonum seeds for 60 days but the count returned to normal after 90 days. Sperm count reduction and atrophic changes in testis and epididymis suggest reduction in male sex hormone that is androgen as the mechanism of anti-fertility effect.[45] The petroleum ether extract proved to retain high estrogenic activity in immature female rats.[46] Petroleum ether extract of C. medica seeds exhibited estrogenic effects in rats which include an increase in uterine weight and vaginal epithelial cell cornification. The opening of vagina on the 5th day and cornification of vaginal epithelial cells was found in 30-day-old immature rats.[47] Alcohol and chloroform extract of Citrus hystrix fruit peels exhibited postcoital anti-fertility activity in pregnant rats.[48] The ethyl acetate fraction of alcoholic extract of C. limonum seeds showed reversible anti-fertility effect in mice by virtue of its anti-zygotic action.[49]C. medica Linn. (peel) was used as the traditional/folkloric medicine for anti-fertility activity.[50],[51]

Anti-hyperglycemic action

Ethanolic extract of C. maxima fruit peels significantly shown their antidiabetic potential by decreasing blood glucose levels and maintaining body weight and serum lipid concentrations to normal.[52] Its stem bark extract possesses significant antidiabetic activity at 400 mg/kg than 200 mg/kg.[53]C. aurantium L. significantly decreases total lipid, total cholesterol, triglycerides, low density lipoprotein cholesterol, and liver enzymes.[54] Methanol extract of C. maxima leaf significantly normalized blood glucose levels, serum biochemical parameters, decreased lipid peroxidation in a dose dependent manner, and recovered glutathione as compared to those of streptozotocin (STZ) control.[55]C. maxima fruit juice has significant glucose tolerance and normal lipid profile in STZ induced type-II diabetic rat.[56] Hypoglycemic effect of essential oil of C. reticulate and its interaction with glibenclamide was evaluated in euglycemic and hyperglycemic rats. The essential oil of C. reticulate exhibited significant hypoglycemic activity while it did not potentiated the hypoglycemic activity of glibenclamide.[57] Intraperitoneal administration of C. sinensis leaf essential oil to diabetic rats led to a significant reduction (P = 0.05) of fasting blood glucose and hepatic glucose levels while hepatic glycogen significantly increased (P = 0.05) when compared to diabetic control animals.[58]

Hypolipidemic activity

Lyophilized juices of C. sinensis L. and C. limon L. Burmese significantly increased high-density lipoprotein (HDL) and lowered cholesterol, low-density lipoprotein, and triglyceride plasma levels in diet-induced rat hypercholesterolemia when administered for 15 days. In particular, C. limon has more marked effect on cholesterol and triglyceride levels, C. sinensis is more able to increase HDL levels. Prolonged use of C. sinensis and C. limon juices determines a considerable protection against insurgency of hypercholesterolemia.[59]

 Conclusion



The traditional and ethno medicinal literature revealed that Citrus plants are very effective in different pathologies. The present review summarizes few pharmacological studies on Citrus species. The plant is found to be potent analgesic, anti-inflammatory, antioxidant, anthelmintic, antibacterial, antifungal agent. The phytoconstituents which are present in the plant are mainly coumarins and flavonoids which are responsible for the actions. More research is needed to isolate the constituents responsible for the biological actions. From the current review of the literature and Ayurvedic text, it can be concluded that the plant has high medicinal value. The phytochemical constituents and isolated bioactive compounds of Citrus genus can be investigated further to achieve lead in developing new herbal drug through reverse pharmacological approaches for treatment of various chronic diseases such as liver diseases, arthritis, cancer, and other inflammatory diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Katcher HI, Hill AM, Lanford JL, Yoo JS, Kris-Etherton PM. Lifestyle approaches and dietary strategies to lower LDL-cholesterol and triglycerides and raise HDL-cholesterol. Endocrinol Metab Clin North Am 2009;38:45-78.
2Van Horn L, McCoin M, Kris-Etherton PM, Burke F, Carson JA, Champagne CM, et al. The evidence for dietary prevention and treatment of cardiovascular disease. J Am Diet Assoc 2008;108:287-331.
3Lücker J, El Tamer MK, Schwab W, Verstappen FW, van der Plas LH, Bouwmeester HJ, et al. Monoterpene biosynthesis in lemon (Citrus limon). cDNA isolation and functional analysis of four monoterpene synthases. Eur J Biochem 2002;269:3160-71.
4Pincemail J, Deby C, Lion Y, Braguet P, Hans P, Drien K, et al. Role of flavonoids in lipoperoxidation and radicalarractions. In: Farkas L, Gabor M, Kallay F, editors. Flavonoids and Bioflavonoids. Proceedings of the 7th Hungraian Bioflavonoid Symposium, Hungary. New York: Elsevier Science Publishers; 1986. p. 423-36.
5Wang PF, Zheng RL. Inhibitions of the autoxidation of linoleic acid by flavonoids in micelles. Chem Phys Lipids 1992;63: 37-40.
6Morel I, Lescoat G, Cogrel P, Sergent O, Pasdeloup N, Brissot P, et al. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 1993;45:13-9.
7Panara K, Joshi K, Nishteswar K. A review on phytochemical and pharmacological properties of Citrus medica Linn. Int J Pharm Biol Arch 2012;3:1292-7.
8Sidana J, Saini V, Dahiya S, Nain P, Bala S. A review on citrus — The boon of nature. Int J Pharm Sci Rev Res 2013;18:20-7.
9Hooker J. The Flora of British India Part I. London, L. Reeve; 1872. p. 514.
10Okwu D. Citrus fruits: A rich source of phytochemicals and their roles in human health. Int J Chem Sci 2008;6:451-71.
11Roger G. New Life Style Enjoy It. Editorial Safelie SL. Spain; 1999. p. 75-6.
12Roger G. Encyclopedia of Medicinal Plants. Vol. 1, Education and Health Library. Editorial Safeliz S.L. Spain; 2002. p. 153-4.
13Silalahi J. Anticancer and health protective properties of citrus fruit components. Asia Pac J Clin Nutr 2002;11:79-84.
14Rauf A, Uddin G, Ali J. Phytochemical analysis and radical scavenging profile of juices of Citrus sinensis, Citrus anrantifolia, and Citrus limonum. Org Med Chem Lett 2014;4:5.
15Nalini A, Chimmad B. Morphological and nutritional characteristics of selected citrus fruits of Uttara Kannada District. Karnataka J Agric Sci 2003;16:533-8.
16Khalid H, Nisar M, Majeed A, Nawaz K, Bhatti K. Ethnomedicinal survey for important plants of Jalalpur Jattan, District Gujrat, Punjab, Pakistan. Ethnobotanical Lealf 2010;14:807-25.
17Jitin R. An ethnobotanical study of medicinal plants in Taindol village, district Jhansi, Region of Bundelkhand, Uttar Pradesh, India. J Med Plants Stud 2013;1:59-71.
18Suryawanshi J. An overview of Citrus aurantium used in treatment of various diseases. Afr J Plant Sci 2011;5:390-5.
19Campêlo LM, de Almeida AA, de Freitas RL, Cerqueira GS, de Sousa GF, Saldanha GB, et al. Antioxidant and antinociceptive effects of Citrus limon essential oil in mice. J Biomed Biotechnol 2011;2011:678673.
20Campêlo LM, Gonçalves FC, Feitosa CM, de Freitas RM. Antioxidant activity of Citrus limon essential oil in mouse hippocampus. Pharm Biol 2011;49:709-15.
21Bertuzzi G, Tirillini B, Angelini P, Venanzoni R. Antioxidative action of Citrus limonum essential Oil on skin. Eur J Med Plants 2013;3:1-9.
22Bhavitavya B, Asdaq S, Asad M, Prasad S. Antiulcer activity of Lemon (Citrus limon) fruit juice and its interaction with conventionally used antiulcer drugs in rats. Nat Prod J 2012;2:61-8.
23Rozza A, Moraes T, Kushima H, Tanimoto A, Bauab M. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E2. Chem Biol Interact 2011;189:82-9.
24Bilal H, Akram W, Ali-Hassan S. Larvicidal Activity of citrus limonoids against Aedes albopictus Larvae. J Arthropod Borne Dis 2012;6:104-11.
25Bidkar J, Bhujbal M, Ghanwat D, Dama G. Anthelmentic activity of Citrus aurantium Linn. IJPRD 2011;3:69-72.
26Bairagi G, Kabra A, Mandade R. Anthelmintic activity of Citrus medica L. leaves in Indian adult earthworm. Int J Pharm Technol Res 2011;3:664-7.
27Siskos EP, Konstantopoulou MA, Mazomenos BE, Jervis M. Insecticidal activity of Citrus aurantium fruit, leaf, and shoot extracts against adult olive fruit flies (Diptera: Tephritidae). J Econ Entomol 2007;100:1215-20.
28Sen S, Bala A, Kar B, Bhattacharya S, Mazumder U, Gupta M. Antitumor potential of Citrus limetta fruit peel in Ehrlich ascites carcinoma bearing Swiss albino mice. Alterns Med Stud 2012;2:e10.
29Patil J, Jayaprakasha G, Chidambara K, Tichy S, Chetti M, Patil B, et al. Apoptosis-mediated proliferation inhibition of human colon cancer cells by volatile principles of Citrus aurantifolia. J Food Chem 2009;114:1351-8.
30Jomaa S, Rahmo A, Alnori A, Chatty M. The cytotoxic effect of essential oil of syrian Citrus limon peel on human colorectal carcinoma cell line (Lim1863). Middle East J Cancer 2012;3: 15-21.
31Shanmugam P, Venkataraman S, Ariamuthu S. Cytoprotective action of Citrus aurantifolia fruit extract against afltoxin-B1 induced cytotoxicity. Int J Res Pharmacol Pharmacother 2013;2:408-13.
32Pradeep M, Wadher T, Gomashe A. Antibacterial activity of Citrus limon fruit juice against clinical isolates of human pathogens. Asian J Microbiol Biotechnol Environ Sci 2007;9:129-32.
33Madhuri S, Hegde A, Srilakshmi N, Prashitha K. Antimicrobial activity of Citrus sinensis and Citrus aurantium peel extracts. JPSI 2014;3:366-8.
34Nada K, Zainab A. Antimicrobial activity of different aqueous lemon extracts. J Appl Pharm Sci 2013;3:74-8.
35Yekeen M, Ajala O, Alarape A. Antifungal activities of Citrus sinensis seed oil against Lentinussajor-caju. Adv Appl Sci Res 2014;5:109-13.
36Shinkafi S, Ndanusa H. Antibacterial activity of Citrus limon on Acne vulgaris (pimples). Int J Sci Invent Today 2013;2:397-409.
37Dhiman A, Nanda A, Ahmad S, Narasimhan B. In vitro antimicrobial status of methanolic extract of Citrus sinensis Linn.fruit peel. Chron Young Sci 2012;3:204-8.
38Guerra F, Mendes J, Oliveira W, Souza F, Trajano V, Coutinho H, et al. Antibacterial activity of the essential oil of Citrus limon against multidrug resistant Acinetobacter strains. Rev Bras Farm 2013;94:142-7.
39Sood S, Bansal S, Muthuraman A, Gill N, Bali M. Therapeutic potential of Citrus medica L. peel extract in carrageenan induced inflammatory pain in rats. Res J Med Plant 2009;3:123-33.
40Sivakumar N, Venkataraman R. Phytochemical and pharmacological studies on plant waste materials. Pharm Sin 2010;1:1-6.
41Sood S, Arora B, Bansal S, Muthuraman A, Gill NS, Arora R, et al. Antioxidant, anti-inflammatory and analgesic potential of the Citrus decumana L. peel extract. Inflammopharmacology 2009;17:267-74.
42Negi S, Anand B. Analgesic activity of fruit decoction of Citrus medica Linn. J Pharm Res 2010;3:2119.
43Casimiro M, Margarita G, Danice R, Judilynn N. Evaluation of the hepatoprotective activity of Citrus microcarpa Bunge (Family Rutaceae) fruit peel against acetaminophen-induced liver damage in male BFAD- Sprague Dawley rats. Int J Chem Environ Eng 2010;1:127-32.
44Bhavsar S, Joshi P, Shah M, Santani D. Investigation into hepatoprotective activity of Citrus limon. Pharm Biol 2007;45:303-11.
45Kulkarni T, Mateenuddin M, Bodhankar S, Saharabudhe R. Reversible anti- fertility effect of lemon seeds (Citrus limonum) in Male Albino Rats. IJRPBS 2012;3:545-50.
46El-Alfy T, Hetta M, Yassin N, Rahman R, Kadry E. Estrogenic activity of Citrus medica L. leaves growing in Egypt. J Appl Pharm Sci 2012;2:180-5.
47Patil SJ, Patil SB. Estrogenic activity of petroleum ether extract of seeds of Citrus medica on immature albino rats. Int J Green Pharm 2008;2:91-4.
48Pawinee P, Thirayudh G, Aporn C. Antifertility effect of Citrus hytrix. J Ethnopharmacol 1985;13:105-10.
49Kulkarni TR, Kothekar MA, Mateenuddin M. Study of anti-fertility effect of lemon seeds (Citrus limonum) in female albino mice. Indian J Physiol Pharmacol 2005;49:305-12.
50Maurya R, Srivastava S, Kulshreshta DK, Gupta CM. Traditional remedies for fertility regulation. Curr Med Chem 2004;11: 1431-50.
51Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Q J Crude Drug Res 1972;12:1922.
52Kharjul M, Gali V, Kharjul A. Antidiabetic potential of ethanolic extracts of Citrus maxima fruit peel and Anvillea garcinii. Int J Pharm Innov 2014;4:8-18.
53Abdul M, Shenoy A, Hegde K, Aamer S, Shabaraya A. Evaluation of the anti-diabetic activity of ethanolic extract of Citrus maxima Stem Bark. IJPCS 2014;3:642-50.
54Osfor M, Hegazy A, El-moaty M, Elmadbouly M, Afify A, Elbahnasawy A. Hypo-cholesterolemic and hypoglycemic effects oforange albedo powder (Citrus aurantium l.) on male albinorats. Int J Nutr Food Sci 2013;2:70-6.
55Sen S, Gupta M, Mazumder U, Haldar P, Saha P, Bhattacharya S, et al. Antihyperglycemic effect and antioxidant property of Citrus maxima leaf in streptozotocin induced Diabetic rats. Diabetol Croat 2011;40-4:113-20.
56Oyedepot A, Babarinde S. Effects of Shaddock (Citrus maxima) fruit juice on glucose tolerance and lipid profile in type-II Diabetic Rats. Chem Sci Trans 2013;2:19-24.
57Kangralkar V, Gavimath C, Jadhav N, Burli S. Potential hypoglycemic effect of essential oil of Citrus reticulata in wistar rats. Int J Pharm Appl 2000;1:6-9.
58Muhammad N, Omoniwa O, Usman L, Omoniwa B. Antihyperglycemic activity of leaf essential oil of Citrus sinensis (L.) Osbeck on alloxan – Induced Diabetic Rats. Ann Rev Res Biol 2013;3:825-34.
59Trovato A, Monforte M, Barbera R, Rossitto A, Galati E, Forestieri A. Effects of fruit juices of Citrus sinensis L. and Citrus limon L. on experimental hypercholesterolemia in the rat. Phytomedicine 1996;2:221-7.