Bijapuraka (Citrus medica)

Recent Research on Bijapuraka (Citrus medica)

• A study is conducted to determine the chemical composition and the antioxidant, anti-inflammatory, and hypoglycemic potential of Citrus medica flowers, leaves, and fruits at two maturity stages. Flowers and leaves were characterized by the highest total phenols and flavonoid content. A declining trend was observed during the maturity of fruits for both phenols and flavonoids. The antioxidant activity was evaluated by Carotene. The bleaching test showed a strong activity for flowers and endocarp of mature fruits. Minichain F et. all. “Phytochemical profile, Antioxidant, Anti-inflammatory and hypoglycemic potential of hydroalcoholic extracts from Citrus medica L. flowers, leaves, and fruits at two maturity stages.” Food Chem Toxicol 2011 Jul: 49 (7): 1549- 55. 
• Aqueous and alcoholic extracts of roots (C. medica L. var. acida Hook.f.) inhibited the growth of Stap, aureus, Kleb. pneumoniae, Prot. mirabilis, Pscudo. aeroginosa, Esch. Coli and Neiss. Gonorrhea (J. Appl. Bacteriol. 1991, 71, 398).
• Soltani, Jalal & Shojaemehr, Mohadeseh & Alamholo, Mostafa. (2020). Investigation of Antibacterial and Antioxidant Activity of Citrus medica L Extract on Human Pathogenic Bacteria. 7. 10. 34172/ ajcmi. 2020. 02. Background: Natural products derived from medicinal plants are a major source of drug preparation and the main basis for the development of pharmaceutical leads. We have aimed to investigate the in vitro antibacterial and antioxidant activity of various extracts of Citrus medica L. against several human pathogenic bacteria. Methods: The plant samples of C. medica L. were collected from Ramsar province, Iran. The gram-positive bacteria Streptococcus pyogenes, Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Enterococcus faecalis, and Staphylococcus aureus, as well as the gram-negative bacteria Escherichia coli, Shigella boydii, Salmonella typhi, Pseudomonas aeruginosa, Enterobacter aerogenes, and Klebsiella pneumoniae were prepared from Bu Ali Sina University, Hamadan, Iran. Agar diffusion assay was applied, and the antioxidant properties of extracts were determined by DPPH assay. Total phenolic and flavonoid contents as well as some compounds such as alkaloids, saponin, and tannin were further analyzed. Results: Results indicated that C. medica extracts possessed antibacterial activity, and that root, seed, and leaf exhibited the highest activities against human pathogens, especially M. luteus. Roots contained the highest total phenolics (106.1 mg GA/ g), while leaves contained the highest total flavonoids (3.24 mg/ g). Leaf methanol extract also contained alkaloids, saponins, and tannins. Conclusions: The antibacterial activities of C. medica extracts could be explained by synthesizing such compounds. Moreover, seed and root extracts of C. medica showed strong radical scavenging activities.
• Okhli, Somayeh & Mirzaei, Habibollah & Hosseini, Ebrahim. (2020). Antioxidant activity of citron peel (Citrus medica L.) essential oil and extract on stabilization of sunflower oil. OCL. 27. 32. 10. 1051/ oct/ 2020022. Due to the unfavorable effects of synthetic antioxidants, the use of various sources of plant antioxidants to prevent food oxidation, especially oil-based or fat-based varieties, has recently received considerable attention. In this study, the antioxidant effect of essential oil and extract from the citron fruit (Citrus medica L.) was investigated on the thermal stability of sunflower oil. Aqueous, ethanolic, and methanolic extracts of citron peel (800 ppm), BHT synthetic antioxidant (200 ppm), and citron peel essential oil (800 ppm) were added to sunflower oil. The oil oxidation stability was evaluated for 5 days by analyzing the values of peroxide, anisidine, thiobarbituric acid, botox, and oxidative stability index (OSI). Results showed that the peroxide, anisidine, and botox values had an increasing trend over time. The effects of storage time, extract, and essential oil were statistically significant in reducing the oxidation rate of sunflower oil during storage. Ultrasonic-assisted ethanolic extract at 30 min showed the highest OSI. The results of this study demonstrated the positive effects of citron peel extract essential oil on sunflower oil stability and its superiority over synthetic antioxidants.
• Sood, S. & Bansal, Stuti & Muthuraman, Arunachalam & Gill, N. & Bali, Manoj. (2009). Therapeutic Potential of Citrus medica L. Peel Extract in Carrageenan Induced Inflammatory Pain in Rat. Research Journal of Medicinal Plants. 3. 123-133. 10. 3923/ rjmp. 2009. 123. 133. In this study, we planned to evaluate the antioxidative, anti-inflammatory, and analgesic potential of Citrus medica peel extract. Antioxidant activity in different solvent systems was evaluated. Ethyl acetate extract of Citrus medica peel (EtCM) showed maximum 1, 1- diphenyl-2- picrylhydrazyl (DPPH) and hydrogen peroxide radical scavenging activity in a dose-dependent manner as compared to ascorbic acid. Further, anti-inflammatory and analgesic activities of Et- CM (200, 300, and 400 mg kg-1) were studied on carrageenan-induced inflammatory pain in rats. Anti-inflammatory activity was assessed by measuring paw volume in rats. Analgesic activity was evaluated for its central and peripheral pharmacological actions by using a hot plate, plantar, pinprick, and mechanical allodynia tests in rats. Et- CM (400 mg kg-1) produced a significant decrease in paw volume and pain as compared to diclofenac. Therefore, the Citrus medica peel extract may be used as a future antioxidant for the treatment of inflammation and pain.
• Nagaraju, B & Anand, S. & Ahmed, Nazeer & Narendra, J & Chandra, Sharath & Ahmed, Faiyaz & Padmavathi, G. (2012). Antiulcer Activity of Aqueous Extract of Citrus medica Linn. Fruit Against Ethanol-Induced Ulcer in Rats. Advances in Biological Research. 6. 24- 29. Citrus medica Linn. (Rutaceae) is known as Gajanimbe and is used as a folk medicine for the treatment of gastric ulcers. The present study was planned to evaluate the antiulcer activity of aqueous extract of the fruits against ethanol-induced ulcers in rats. The extract was subjected to phytochemical screening and found to contain carbohydrates, proteins, amino acids, and flavonoids. The rats were pretreated with the extract at two doses (250 and 500 mg kg/ G p.o.) and the antiulcer effect was compared with that of ranitidine (20 mg kg/ G p.o.). 1 1 The extract of both doses showed a significant reduction in ulcer formation. Histopathological sections showed a significant decrease in mucosal ulceration, inflammatory mucosal changes, and submucosal edema compared to ethanol treated group and the ranitidine group. It is concluded that the fruits of C. medica possess significant antiulcer activity against ethanol-induced ulcers in rats and the antiulcer activity could be due to the presence of flavonoids as these compounds have well-documented antiulcer activity.
• Panara, Kalpesh & Nishteswar, K. & Nariya, Mukeshkumar. (2021). The sedative and hypnotic activity of the leaves of Bijapura (Citrus medica L.). Indian Journal of Natural Products and Resources. 12. 605- 609. Bijapura (Citrus medica L., family: Rutaceae) leaves powder when used along with honey is documented in ancient text to induce sleep and is useful in patients with insomnia. The purpose of the present research work was to investigate the sedative and hypnotic effects of C. medica leaves powder along with honey as anupana (adjuvant) in experimental animals. The effects of leaf powder on the locomotor activity of albino rats were evaluated using an open-field test. The hypnotic effect was evaluated by potentiation of pentobarbital-induced sleep test and muscle relaxant activity by Rotarod test using Swiss albino mice. Results were analyzed with one-way ANOVA and post-hoc Tukey’s t-test with P < 0.05 as significant. The leaf powder along with honey significantly (P < 0.01 and P < 0.05) reduced the numbers of square crossed and locomotor activity in the Open field test when compared to control and vehicle control groups. It significantly (P < 0.05) potentiated the pentobarbitone-induced sleep duration when compared to the control group. However, the leaf powder did not reduce or affect the latency of the fall-off time of mice in the Rotarod test. Vehicles such as honey failed to produce significant effects when compared to the control group, whereas standard drugs such as diazepam produced significant sedative, hypnotic, and muscle relaxant activity in albino mice. The result suggests that C. medica leaves powder has sedative and hypnotic activity without affecting the muscle tone/coordination in animals and thus, proves its traditional claim in insomnia.
• Menichini, Federica & Loizzo, Monica & Bonesi, Marco & Conforti, Filomena & Luca, Damiano & Statti, Giancarlo & De Cindio, Bruno & Menichini, Francesco & Tundis, Rosa. (2011). Phytochemical profile, antioxidant, anti-inflammatory, and hypoglycemic potential of hydroalcoholic extracts from Citrus medica L. cv Diamante flowers, leaves, and fruits at two maturity stages. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 49. 1549- 1555. 10. 1016/ j. ft. 2011. 03. 048. Since the past decade consumption of certain foods has been reported to have a positive effect on health. The object of the study was to determine for the first time the chemical composition and the antioxidant, anti-inflammatory, and hypoglycemic potential of Citrus medica L. cv Diamante flowers, leaves, and fruits (endocarp and mesocarp) at two maturity stages. Flowers and leaves were characterized by the highest total phenols and flavonoid content. A declining trend was observed during maturity of fruits for both phenols and flavonoids. The antioxidant activity evaluated by the β-carotene bleaching test showed a strong activity for flowers and endocarp of mature fruits with IC50 values of 2.8 μg/ mL and 3.5 μg/ mL, respectively, after 30 min of incubation. Interestingly, the mature fruits’ endocarp (IC50 value of 426.0 μg/ mL) could inhibit α-amylase with an IC50 value 2-fold higher than immature fruits. None of the tested extracts affected the proliferation of human skin fibroblasts 142- BR. The obtained results suggest a potential use of C. medica L. cv Diamante as a new valuable Citrus species with functional properties for food or nutraceutical products based on the high content of phytochemicals.
• Luo, Bi & Lv, Jia & Li, Kejie & Liao, Peiran & Chen, Peng. (2022). Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide from Citrus medica L. var. sarcodactylis. Frontiers in Nutrition. 9. 916976. 10. 3389/fruit. 2022. 916976. This study aimed to extract polysaccharides from Citrus medica L. var. sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. A new polysaccharide named K- CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE- 52 cellulose column chromatography with an average molecular weight of 3.76 × 103 k- Da. Monosaccharide composition analysis revealed that K- CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75: 5.87: 1.00. Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K- CLMP was alternately connected with 1, 2- Rha and 1, 4- Gal to form the backbone, and a small number of glucose residues was connected to O- 4 of rhamnose. The results of DPPH⋅ and ABTS+⋅ radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. polysaccharide (CMLP) and K- CLMP exhibited strong free-radical-scavenging properties in a dose-dependent manner. In addition, K- CMLP significantly inhibited the production of pro-inflammatory cytokines (IL- 6 and TNF- α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. These results provide a basis for further use as one of the potential functions of food or natural medicine.
• Sah, Archana & Juyal, Vijay & Melkani, Anand. (2011). Antimicrobial Activity of Six Different Parts of the Plant Citrus medica Linn. Pharmacognosy Journal. 3. 80– 83. 10. 5530/ pj. 2011. 21. 15. Introduction: Antimicrobial activity of fruit juice and ethanolic extracts of root, leaf, bark, peel, and pulp of citron (Citrus medica Linn., Rutaceae) was examined against seven bacteria (Bacillus subtilis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus vulgaris), two fungi (Aspergillus flavus and A. niger) and a yeast Candida albicans of clinical origin. Methods: The level of antimicrobial effects was established using an in vitro disc diffusion method; minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined by the standard agar dilution method. Results: All extracts and fruit juice showed varied levels of antibacterial activity against one or more test bacteria. Antifungal activity was shown by only root extract and fruit juice while C. albicans were resistant to all tested plant samples. Broad spectrum antimicrobial activity was shown by fruit juice (MIC <1 % to 3.5 % and MBC 1 % to 7 % v/v) and fruit pulp (MIC 25 mg/ ml and MBC 30 to 75 mg/ml). Root extract was found to be highly potent with MIC as small as 0.5 mg/ml and MBC 1 mg/ ml against S. aureus. Among all tested plant samples leaf and peel extracts have shown less antimicrobial activity. Conclusion: It is concluded that fruit juice and juiceless fruit pulp extract have shown broad antimicrobial activity while root extract was very effective against some tested microorganisms.
• Bukhari, Associate Prof. Dr. Syed Nasir Abbas & Alamgeer & Saeed, Sumera & Asim, Mulazim & Irfan, Hafiz & Ejaz, Hasan & Elsherif, Mervat & Junaid, Kashaf. (2022). Antihypertensive and Vasorelaxant Effects of Citrus aurantifolia Linn. Fruit: Proposed Mechanisms. Evidence-Based Complementary and Alternative Medicine. 2022. 10. 1155/ 2022/ 5871424. Background: Citrus aurantifolia Linn. fruit, a natural dietary item, has long been used traditionally to treat hypertension in Pakistan. The current research work aims to explore the effect on blood pressure and its mechanisms. Methods: The aqueous methanol extract of plant fruit was used to evaluate hypotensive/antihypertensive, vasorelaxation, and safety profiles. Moreover, the in vitro inhibitory effect of AMECA on phosphodiesterase was also evaluated. Results:  In hypotensive studies, extracts of Citrus aurantifolia fruit exhibited a concentration-dependent reduction in SBP, DBP, MAP, and heart rate. A similar effect has been observed on anesthetized rats, but the effects exerted by the extract were not altered significantly in the presence of L- NAME, atropine, captopril, and propranolol. Moreover, in coronary arteries, the extract significantly potentiates relaxations induced by cGMP- and cAMP-dependent relaxing agonists. When exposed to PDEs, the extract concentration-dependently subdued cGMP-hydrolyzing activity of different PDEs with IC50 values of 40- 130 μg/ mL. Conclusion:  It is conceivable that extracts obtained from Citrus aurantifolia fruit produced hypotensive and antihypertensive effects in rats. The extract elicited endothelium-independent vasorelaxation, possibly by acting directly on smooth muscles of the coronary artery and by increasing cGMP and cAMP via nonselective inhibition of vascular PDEs.
• Entezari, Maliheh & Majd, Ahmad & Falahian, Fathollah & Mehrabian, Sedigheh & Hashemi, Mehrdad & Ardeshirylajimi, Abdolreza. (2009). Antimutagenicity and Anticancer Effects of Citrus Medica Fruit Juice. Acta Medica Iranica. 47. 373- 377. Currently, cancer is considered one of the main factors of mortality globally. Many chemicals in our environment can cause genetic mutations and are potentially responsible for millions of cancer-related deaths. Nowadays scientists are looking for food materials that can potentially prevent cancer from occurring. The purpose of this research is to examine the anti-mutagenicity anticancer effect of Citrus Medica fruit juice. In the present study, human astrocytoma cancer cells were cultured in DMEM (Gibco), supplemented with 10 % fetal calf serum, penicillin-streptomycin, L- glutamine and incubated at 37 ºC for 2 days. In addition, cancer cell lines were treated with half-ripe and ripe Citrus Medica fruit juice, and cellular vital capacity was determined by MTT. The Citrus Medica fruit juice was subsequently evaluated in terms of antimutagenicity and anticancer properties by a standard reverse mutation assay (Ames Test). This was performed with a histidine auxotroph strain of Salmonella typhimurium (TA100). Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when exposed to a carcinogen substance (Sodium Azide). During MTT, the human astrocytoma cell line was revealed to have a meaningful cell death when compared with controls (P< 0.01). In the Ames Test the fruit juice prevented the reverted mutations and the hindrance percent of half-ripe Citrus Medica was 71.7 % and ripe Citrus Medica was 34.4 % in anti- mutagenicity test and this value in anti- cancer test was 83.3% and 50 % in half- ripe Citrus Medica and ripe Citrus Medica respectively. This is the first study that has revealed antimutagenicity and anticancer effects of Citrus Medica fruit juice.
• Bairagi, G. & Kabra, A.O. & Mandade, R. (2011). Anthelmintic activity of citrus medica L. leaves in Indian adult earthworm. International Journal of PharmTech Research. 3. 664- 667. Citrus medica L. popularly known as ‘Bara nimbu’ in India belongs to the family Rutaceae. The objective of the present work was to evaluate the in-vitro anthelmintic potency of the petroleum ether extract of Citrus medica leaves using Indian earthworms (Pheretima posthumad). The various concentrations (20- 80 mg/ ml) of the petroleum ether extract were tested in vitro for anthelmintic potency by determining the time of paralysis and time of death of the worm. Piperazine citrate (15 mg/ ml) used as standard. The result of the present study indicates that Citrus medica L. potentiates to paralyze earthworms and also causes their death after some time. The shortest time of paralysis and time of death was observed at a higher dose (80 mg/ ml) of petroleum ether extract was found to be 30.86 min. Thus, the present study demonstrates that Citrus medica as an anthelmintic has been confirmed as the petroleum ether extracts of leaves displayed activity against the earthworm used in the study.
• Conforti, Filomena & Statti, Giancarlo & Tundis, Rosa & Loizzo, Monica & Menichini, Francesco. (2007). In vitro activities of Citrus medica L. cv. Diamante (Diamante citron) is relevant to the treatment of diabetes and Alzheimer’s disease. Phytotherapy research: PTR. 21. 427- 33. 10. 1002/ ptr. 2077. The present study showed for the first time the in vitro properties (antioxidant, hypoglycaemic, and anticholinesterase) of Citrus medica L. cv. Diamante which belongs to the Rutaceae family. The n-hexane extract of Diamante citron peel is characterized by the presence of monoterpenes and sesquiterpenes. The most abundant constituents were two monoterpenes: limonene and gamma-terpinene. The extract showed significant antioxidant activity that was carried out using different assays (DPPH test, beta-carotene bleaching test, and bovine brain peroxidation assay). Oxidative damage, caused by the action of free radicals, may initiate and promote the progression of several chronic diseases, including diabetes and Alzheimer’s disease. Diamante citron peel extract showed hypoglycaemic activity and an anticholinesterase effect.

Recent Research on Madhukarkati (Citrus decumana)

• Sood, Shailja & Muthuraman, Arunachalam & Arora, Bhawna & Bansal, Stuti & Bali, Manoj & Sharma, Pritam. (2010). Potential Effect of Citrus decumana Extract on Stress-Induced Peptic Ulcer in Rat. Latin American Journal of Pharmacy. 29. 52- 56. The present study was designed to investigate the antiulcer activity of ethyl acetate extract of Citrus decumana (grapefruit) peels. The antiulcerogenic activity was evaluated in water immersion and hypothermic restraint stress models at different doses (150, 250, and 350 mg/ kg). The antiulcer potential of the extract was assessed by determining and comparing the ulcerative index and biochemical estimation was carried out using various oxidative stress markers i.e., TBARS, GSH, SOD, and CAT in the blood and tissue samples. The highest dose (350 mg/kg) of the extract showed a significant decrease in the ulcerative index and TBARS level, whereas there was an increase in the GSH, SOD, and CAT levels. Whereas the lowest and medium doses (150 mg/ kg and 250mg/ kg) did not produce any significant results. Therefore, our study indicates that the Citrus decumana peel extract may be used as a natural therapeutic agent in the treatment of peptic ulcers.
• Sood, Shailja & Arora, Bhawna & Bansal, Stuti & Muthuraman, Arunachalam & Gill, Naresh & Arora, Rajendra & Bali, Manoj & Sharma, Pritam. (2009). Antioxidant, anti-inflammatory, and analgesic potential of the Citrus decumana L. peel extract. Inflammopharmacology. 17. 267- 74. 10. 1007/ s10787- 009-0015- y. The present study was designed to investigate the antioxidant, anti-inflammatory, and analgesic potential of Citrus decumana peel extract. The antioxidant activity of Citrus decumana peel extract in four solvent systems was evaluated by 1,1- diphenyl- 2- picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) radical scavenging methods. Ethyl acetate peel extract of Citrus decumana (EtCD) was studied for its anti-inflammatory and analgesic activities at a dose level of 100, 200, and 300 mg/ kg. Anti-inflammatory activity was performed using carrageenan-induced paw edema in rats. Analgesic activity was evaluated for its central and peripheral pharmacological actions in mice. EtCD showed significant antioxidant activity in a dose-dependent manner when compared with ascorbic acid. EtCD at the dose of 300 mg/kg produced a significant decrease in paw volume and pain when compared with the reference drugs diclofenac and morphine, respectively. The Citrus decumana peel extract may be useful as a natural antioxidant in the treatment of inflammation and pain.
• Mishra, Arun & Kumar, Arvind. (2017). Pharmacological Applications of Diphenylamine and Its Derivative as Potent Bioactive Compound: A Review. Current Bioactive Compounds. 13. 1- 1. 10. 2174/ 157340721- 3666170301155550. In 1863, Diphenylamine (DPA) was prepared by Hoffmann by the destructive distillation of different triphenylmethane dyes. DPA are naturally occurring compounds, present in onions, leaves of black and green tea, and peel of citrus fruits. DPA derivatives belong to the category of Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Diclofenac, chemically called 2- (2, 6- dichloranilino) phenylacetic acid, is a well-known NSAID. Other important compounds are tolfenamic acid, flufenamic acid, and mefenamic acid, etc. DPA derivatives are claimed to have several important biological activities which include anti-microbial, analgesic, anti-inflammatory, anti-convulsant, and anti-cancer activities. Many more compounds have been discovered and many are still being focused. The key goal of this article is to show the different derivatives and the pharmacological activities of DPA. Hence, it can be concluded that DPA and its derivatives possess significant therapeutic functions, and many potent derivatives are still to be discovered.
• Sood, Shailja & Muthuraman, Arunachalam & Gill, Naresh & Bali, Manoj & Sharma, Pritam. (2010). Role of 7, 8- dimethoxy- coumarin in anti-secretary and anti-inflammatory action on pyloric ligation-induced gastritis in rats. Journal of Asian natural products research. 12. 593- 9. 10. 1080/ 10286020. 2010. 486377. The present study was designed to investigate the effect of 7, 8-dimethoxycoumarin (DMC) isolated from ethyl acetate extract of Citrus decumana peels on gastritis in rats. Isolation of 7, 8- DMC from ethyl acetate extract of C. decumana peels was done by column and preparative thin layer chromatography using different solvents on a polarity basis. Furthermore, the effect of 7, 8- DMC (50, 75, and 100 mg/ kg, i.p.) in pyloric ligation-induced gastritis was studied in rats. The highest dose of 7, 8- DMC showed a significant decrease in the gastric volume, total acidity, ulcerative index, thiobarbituric acid reactive species levels, and myeloperoxidase activity, whereas there was an increase in the glutathione level. However, the lowest and medium doses did not produce significant results as compared to omeprazole and N-acetyl cysteine-treated groups. Compound 7, 8- DMC (100 mg/ kg) showed an ameliorative effect on gastric inflammation and may be used as a therapeutic agent in the treatment of gastritis.
• Bear, Wayne & Teel, R. (2000). Effects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the In vitro metabolism of the tobacco-specific nitrosamine NNK. Anticancer research. 20. 3323-  9. NNK is a potent environmental carcinogen to which both smokers and nonsmokers are exposed. The response to NNK may be affected by factors including nutrition. We investigated the effects of five citrus phytochemicals on the in vitro metabolism of the tobacco-specific nitrosamine NNK and on the dealkylation of methoxy-resorufin (MROD) and peroxy- resorufin (PROD) in liver and lung microsomes of the Syrian golden hamster. In the NNK metabolism experiments in vitro, incubations contained 3 microCi [5- H3] NNK, 0.5 mg microsomal protein, and 0.5 mole of the citrus phytochemical diosmin, naringin, naringenin, quercetin or rutin. In the dealkylation studies incubations contained 0.5 microM methoxy-resorufin or pentoxyresorufin, 0.5 mg microsomal protein, and 0.5 mole of citrus phytochemicals. The major NNK metabolism pathway in hamster liver microsomes was NNK- reduction while in lung microsomes it was alpha-hydroxylation. The alpha-hydroxylation pathway produces metabolic products that methylate and pyridyloxobutylate DNA. Naringenin, a metabolite of naringin, and quercetin were the most potent inhibitors of alpha-hydroxylation of NNK in both liver and lung microsomes. This inhibition correlated with a potent inhibition of MROD and PROD activity in the liver but not in lung microsomes. The metabolic activation of NNK is associated with cytochrome P450 isoforms 1A1, 1A2, 2B1, 2D6 and 2E1. Our results suggest that naringenin and quercetin from citrus fruits inhibit the activity of cytochrome P450 (CYP) isoforms that activate NNK and may afford protection against NNK-induced carcinogenesis.
• Adkar-Purushothama, Charith Raj & Sreenivasa, M. & Prasad, M.N. & Maheshwara, P.K. & Gottravalli Ramanayaka, Janardhana. (2011). First report on Citrus tristeza virus associated with stem-pitting of Citrus decumana in India. Journal of Plant Pathology. 93. Citrus tristeza virus (CTV), genus Closterovirus, family Closteroviridae, occurs in all citrus-growing regions of the world. According to the virus strain, infection results in a variety of symptoms, such as stem pitting, seedling yellows, vein clearing, decline, and, ultimately, tree death. Recently, a stem pitting condition on the scion was observed in Citrus decumana, a species grown in southeastern Asia for fruit production and as a traditional medicinal plant. Leaf samples were collected from symptomatic trees in the Kodagu region of Karnataka (India) and were analyzed for the presence of CTV. Total nucleic acids were extracted from leaf tissues according to Adkar-Purushothama et al. (2007) and analyzed by RT- PCR as described previously (Huang et al., 2004). The expected 672 bp product was amplified. From all symptomatic samples. Two amplicons were cloned and shown to have identical sequences that were deposited in GenBank under accession No. HM853684. Nucleotide sequence analysis indicated 91- 99% identity of the CTV isolates from C. decumana and other isolates from various citrus species from northeastern India.
• Meera, & Kalidhar, S. (2008). A New coumarin from Citrus paradisi Macf. Indian journal of pharmaceutical sciences. 70. 517- 9. 10. 4103/ 0250-474X. 44608. Phytochemical examination of the peel of grapefruit resulted in the isolation of five compounds namely friedelin, beta-sitosterol, 7 (3′, 7′, 11′, 14′-tetramethy) pentadec- 2′, 6′, 10′- trienyloxycoumarin, limonin and cordialin B. These compounds have been characterized based on spectral data, and 7  (3′, 7′, 11′, 14′- tetramethyl) pentadec- 2′, 6′, 10′- trienyloxy- coumarin is a hitherto unreported compound.
• Pantsulaia, Ia & Iobadze, Manana & Pantsulaia, Nato & Chikovani, Tinatin. (2014). The Effect of Citrus Peel Extracts on Cytokines Levels and T Regulatory Cells in Acute Liver Injury. BioMed research is international. 2014. 127879. 10. 1155/ 2014/ 127879. Background: T-cell-mediated immune responses contribute to hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for the prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of an antioxidant, anti-inflammatory mixture of citrus peel extract (CPE) on immune-mediated liver injury. Methods:  The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring the frequency of T regulatory cells (Tregs), cytokines (TNF- α, IL- 10, and IFN- γ), and nitric oxide levels. Results:  The CPE application notably prevents the development of liver injury through decreasing levels of both cytokines (TNF- alpha, INF) and regulatory T cells and increased levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in an evident reduction of liver damage. Conclusion:  Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A-induced hepatitis. The low dose of CPE most likely can be used for the treatment of T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.

Recent Research on Jambir (Citrus limon)

• Dara, Hareesh & Siva, Dinesh & Ravichander, Thatipelli. (2017). Evaluation of Analgesic and Anti-Inflammatory Activity of Citrus Limon Peel in Albino Wistar Rats. International Journal of Medicine and Pharmaceutical Sciences. 5. 59- 63. The lemon [Citrus limon (L.) Rutaceae] exhibits many important natural chemical components, including citric acid, ascorbic acid, minerals, and phenolic compounds, such as flavonoids. Although their biological properties have always been associated with their content of vitamin C, it has recently been shown that flavonoids are other nutrients and non-nutrients (vitamins, minerals, dietary fiber, essential oils, and carotenoids). Therefore, their health-promoting effects, such as obesity, diabetes, blood lipid-lowering, cardiovascular diseases, brain disorders, and certain types of cancer, have been associated with their contents, especially vitamin C and flavonoids, due to their natural antioxidant characteristics. Therefore, this work was designed based on phytochemical constitutions such as flavonoids in Citrus limon peel extracts because flavonoids are rich in the treatment for evaluation of analgesic and anti-inflammatory activity in rats. Fresh and crushed peels of Citrus limon were collected and then extracted with different solvents such as water, alcohol, and methanol at the doses of 100 mg/ kg, and 200 mg/ kg body weight in experimental animal models. Analgesic activity was evaluated by Hotplate and tail-flick method in albino Wistar rats; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw edema and formalin-induced paw edema in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the aqueous, alcoholic, and methanolic extracts of Citrus limon demonstrated significant analgesic and anti-inflammatory activities in the tested models.
• Abdelkader, Basli & Sonia, Tighzert & Nawel, Ibelhoulen & Khettal, Bachra & Madani, Khodir. (2016). In vitro Antioxidant and Anti-Inflammatory Activities of Peel and Peeled Fruits Citrus limon. Current Nutrition & Food Science. 12. 1- 1. 10. 2174/ 1573401312666160822103727. Background: Citrus is the name given to trees belonging to the family of Rutaceae including several species of plants that produce edible fruits providing an appreciable content of several interesting bioactive constituents. In traditional medicine, they are often used as antipyretic, anti-inflammatory, sedative, and antitoxic agents. Our primary aim is to assess the antioxidant ability and anti-inflammatory activity of peel and peeled fruit from Citrus limon. Methods: Ethanolic extracts of peel and peeled fruit of Citrus limon (lemon) were used to investigate antioxidant and anti-inflammatory activities. Total phenolic content was assessed using the Folin-Ciocalteux method. The antioxidant potential was found by measuring the scavenging activity of DPPH and ABTS radicals. Three methods have been adopted to evaluate the in-vitro anti-inflammatory effect of bovine albumin denaturation, lipoxygenase inhibition, and erythrocyte membrane stabilization. Diclofenac as a reference control drug has been used for the study of anti-inflammatory activity. Results: Peels of lemon revealed significantly higher total phenolic content than peeled fruit fraction. Two parts of lemon have shown potent scavenging activity in both DPPH and ABTS methods. Peels and peeled fruit exhibited significant maximum inhibition of protein denaturation in concentration-dependent inhibition manner. The hypotonicity-induced hemolysis as well as the anti-lipoxygenase activities of two parts of lemon have proved significant inhibition at the concentration range of 100- 500μg/ mL. Likewise, diclofenac showed the highest inhibition for all anti-inflammatory assays. Conclusion: Peel and peeled fruit of Citrus limon extracts can be an important source of anti-inflammatory agents.
• Shuaib, Mustafa & Shailabi, Taher & Borwis, Elham & Muhammed, Akram. (2021). Antimicrobial Activity Evaluation of Citrus Lemon Against Streptococcus Pyogenes and Escherichia Coli. 11. 11-16. Background: The therapeutic activities of citrus lemon have been reported in several studies including anti-microbial, anti-inflammatory, antiparasitic, and anticancer activities. Objectives: To determine the potential antimicrobial activity of ethanol and methanol extracts of citrus lemon peel and lemon juice in inhibiting bacterial isolates. Methods and Materials: The antimicrobial effects of citrus lemon alcoholic extracts of peel and juice against Gram-positive (Streptococcus pyogenes) and Gram-negative (Escherichia coli) bacterial isolates were studied. Results: Citrus limon juice has antimicrobial activities more than alcoholic extracts on both bacterial isolates with Escherichia coli 15mm and Streptococcus pyogenes 20mm. The ethanol and methanol extracts of citrus limon peel showed 5 mm and 6 mm of the average inhibition zone against Escherichia coli respectively. On the other hand, the study showed no inhibition effect of both alcoholic extracts on Streptococcus pyogenes. Conclusion: This study demonstrated that citrus lemon juice can be used as a potential source for controlling Streptococcus pyogenes and Escherichia coli growth.
• Miller, Edward & Porter, Jo & Binnie, William & Guo, Ingrid & Hasegawa, Shin. (2004). Further Studies on the Anticancer Activity of Citrus Limonoids. Journal of agricultural and food chemistry. 52. 4908- 12. 10. 1021/ jf049698g. Research in this laboratory has shown that some citrus limonoids can inhibit the development of 7, 12-dimethylbenz[a]- anthracene-induced oral tumors. The data from these studies have suggested that certain rings in the limonoid nucleus may be critical to antineoplastic activity. Using the hamster cheek pouch model, three new limonoids (ichangensin, deoxy limonin, and obacunone) have now been tested for cancer chemopreventive activity. In the first experiment, it was found that the treatments with ichangensin did not affect tumor number or burden. In the second experiment, obacunone reduced tumor number and burden by 25 and 40%, respectively, whereas deoxylimonin reduced tumor number and burden by 30 and 50%, respectively. The results with deoxylimonin were significant, p < 0.05. Overall, the data indicated that changes in the A ring of the limonoid nucleus can lead to a loss of anticancer activity, whereas changes in the D ring can be tolerated without any apparent loss of biological activity.
• Mojtahedin, Ali & Seyedsharifi, Reza & Boustan, Azade. (2016). Evaluation of the antioxidant activity of Citrus limon L. essential oil and its effect on some blood parameters in Moghani sheep. 14. 10. 7537/ marsnsj- 141216.17. Background and objectives: Plant food additives have received widespread attention in recent years. Plants have different components such as essential oils. The citrus family is known as an antioxidant resource. Citrus limon among the citrus family contains limonoids, flavonoids, and phenolic compounds. Regarding this point that there is little research about using Citrus limon essential oil in ruminant nutrition, the aims of this study were the evaluation of the antioxidant activity of Citrus limon and the effect of different levels of this essential oil on some blood parameters of Moghani sheep. Materials and methods: In this study, 6 lactating Moghani sheep were allocated to 3 × 3 Latin square designs with three diets in twenty-one-day periods, seventeen days for adaptation, and four days for sampling. Dietary treatments included: Treatment 1: control diet, treatment 2: control diet with 150 mg essential oil per day, and Treatment 3: control diet with 300 mg essential oil per day. To evaluate the antioxidant effect of the essential oil, sustainable elimination of free radicals by 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) method was used. Blood profiles included glucose, blood urea nitrogen, albumin, total protein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglycerides, and very low-density lipoprotein (VLDL) were also measured. Results: The antioxidant activity of essential oils at doses of 27.5, 55, 110, 220, and 480 mg/ ml were 5, 8, 21, 49, and 85 percent, respectively. In this study, experimental treatments did not affect glucose, blood urea nitrogen, albumin, total protein, or low-density lipoprotein, while increasing the concentration of high-density lipoprotein. Cholesterol, triglycerides, and very low-density lipoprotein were decreased by our treatments significantly (P < 0.05). Conclusion: According to the results of this research, the evaluation of the antioxidant effect of Citrus limon using the DPPH method showed that the antioxidant effect of Citrus limon in free radical removal is strong. In addition, this essential oil has a decreasing effect on the blood plasma lipids. [Ali Mojtahedin, Reza Seyedsharifi, Azadeh Boustan. Evaluation of the antioxidant activity of Citrus limon L. essential oil and its effect on some blood parameters in Moghani sheep. Nat Sci 2016; 14 (12): 108- 113]. ISSN 1545- 0740. ISSN 2375-7167. www. sciencepub. Net/ nature. 
• Oboh, Ganiyu & Bello, Fatai & Ademosun, Ayokunle & Akinyemi, Ayodele & Adewuni, Taiwo. (2015). Antioxidant, hypolipidemic, and anti-angiotensin-1-converting enzyme properties of lemon (Citrus limon) and lime (Citrus aurantifolia) juices. Comparative Clinical Pathology. 24. 10. 1007/ s00580- 015- 2088- x. Lemon (Citrus limon) and lime (Citrus aurantifolia) juices are used in folk medicine for the management of hypertension and other cardiovascular diseases, but the mechanism of action by which they exert their therapeutic action is unclear. The aim of this study is to investigate the effect of lemon and lime juices on angiotensin-1-converting enzyme (ACE) activity in vitro and investigate the hypocholesterolemic properties of the juices in a high-cholesterol diet rat model. The phenolic content and antioxidant properties of the manually squeezed juices were also determined. Lemon juice had a higher total phenol content (64.5 mg/l), while lime juice had a higher total flavonoid content (29.5 mg/l). Both juices inhibited ACE activity in a dose-dependent manner and also exhibited antioxidant activities as typified by their ferric-reducing power, and radicals (DPPH, ABTS, OH, and NO) scavenging abilities, as well as inhibition of Fe2+- and sodium nitroprusside-induced lipid peroxidation in rat’s liver in vitro. The administration of the juices to rats fed with a high-cholesterol diet caused a significant reduction in plasma total cholesterol, triglyceride, and LDL-cholesterol levels and an increase in plasma HDL- cholesterol levels. The inhibition of ACE activity in vitro and in vivo hypocholesterolemic effect of the juices could explain the use of the juices in the management of cardiovascular diseases.
• Raimondo, Stefania & Naselli, Flores & Fontana, Simona & Monteleone, Francesca & Lo Dico, Alessia & Saieva, Laura & Zito, Giovanni & Flugy, Anna & Manno, Mauro & Bella, Maria & Leo, Giacomo & Alessandro, Riccardo. (2015). Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget. 6. 10. 18632/ oncotarget. 4004. Nanosized vesicles are considered key playecell-to-cello cell communication, thus influencing physiological and pathological processes, including cancer. Nanovesicles have also been found in edible plants and have shown therapeutic activity in inflammatory bowel diseases; however, information on their role in affecting cancer progression is missing. Our study identifies for the first time a fraction of vesicles from lemon juice (Citrus limon L.), obtained as a result of different ultracentrifugation, with density ranging from 1, 15 to 1, 19 g/ ml and specific proteomic profile. By using an in vitro approach, we show that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death. Furthermore, we demonstrate that lemon nanovesicles suppress CML tumor growth in vivo by specifically reaching the tumor site and by activating TRAIL-mediated apoptotic cell processes. Overall, this study suggests the possible use of plant-edible nanovesicles as a feasible approach to cancer treatment.
• Campelo, Lidianne & Almeida, Antonia & Freitas, Rizangela & Cerqueira, Gilberto & Sousa, G.F. & Saldanha, Gláucio & Feitosa, Chistiane & Freitas, Rivelilson. (2011). Antioxidant and Antinociceptive Effects of Citrus limon Essential Oil in Mice. Journal of biomedicine & biotechnology. 2011. 678673. 10. 1155/ 2011/ 678673. The antioxidant and antinociceptive activities of Citrus limon essential oil (EO) were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/ kg) significantly reduced the number of writhes, and, at the highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses), this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO.
• Riaz, Azra & Khan, Rafeeq & Mirza, Talat & Mustansir, Tazeen & Ahmed, Mansoor. (2014). In vitro/in vivo effect of Citrus limon (L. Burm. f.) juice on blood parameters, coagulation and anticoagulation factors in rabbits. Pakistan journal of pharmaceutical sciences. 27. 907- 915. The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia, and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have the highest antimicrobial activity. It is used as an antidote against certain venom, due to its platelet inhibitory effect and is also reported to have hypo- hypocholesterolemic effect. However, its anticoagulant and thrombolytic effect were not investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation, and anticoagulation factors. In-vitro tests revealed a highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however, prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg, and 0.6ml/kg in healthy rabbits. Significant changes were observed in hematological parameters such as erythrocytes, hemoglobin and mean corpuscular hemoglobin concentration. Bleeding time and thrombin time were significantly prolonged and there was an increase in protein C and thrombin antithrombin complex levels. These results may be due to the inactivation of thrombin because it significantly decreases fibrinogen concentration and inhibits platelet aggregation. Citrus limon showed maximal anticoagulant effect at 0.4 ml/ kg, which suggests that Citrus limon possesses an anti-thrombin component and could prevent thrombosis playing a cardio-protective role.
• Wu, Chih-Chung & Huang, Yu-Wen & Hou, Chih-Yao & Chen, Ya-Ting & Dong, Cheng-Di & Chen, Chiu-Wen & Singhania, Reeta & Leang, Jie-Yin & Hsieh, Shu-Ling. (2021). The Anti-Obesity Effects of Lemon Fermented Products in 3T3- L1 Preadipocytes and in a Rat Model with High-Calorie Diet-Induced Obesity. Nutrients. 13. 10. 3390/ nu13082809. Lemon (Citrus limon) has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon-fermented product (LFP) which is lemon fermented with Lactobacillus OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3- L1 adipocytes is examined using a Wistar rat model fed a high-fat diet to verify the anti-obesity efficacy and mechanism of LFP. Here, it was observed that LFP reduced cell proliferation and inhibited the lipid accumulation (8.3 %) of 3T3- L1 adipocytes. Additionally, LFP reduced body weight (9.7 %) and fat tissue weight (25.7 %) of rats; reduced serum TG (17.0 %), FFA (17.9 %), glucose (29.3 %), and ketone body (6.8 %); and increased serum HDL-C (17.6 %) and lipase activity (17.8 %). LFP regulated the mRNA expression of genes related to lipid metabolism (PPARγ, C/EBPα, SREBP-1c, HSL, ATGL, FAS, and AMPK). Therefore, LFP reduces body weight and lipid accumulation by regulating the mRNA expression of genes related to lipid metabolism. Overall, our results implicate LFP as a potential dietary supplement for the prevention of obesity.
• Dewanti, Dewa & Ernawati, Desak & Indrayani, Agung & Dewi, Sucindra & Jawi, I Made. (2020). Protective Effect of Lemon (Citrus limon L.) Ethanol Extract Cream as an Antioxidant Against Exposure to Ultraviolet B Rays in the Skin of Male Wistar (Rattus norvegicus) Rats. Jurnal Epidemiologi Kesehatan Komunitas. 5. 8- 14. 10. 14710/ jekk. v5i1. 6910. Background: Indonesia is an archipelagic tropical country that gets sun exposure all the time. Exposure to radiation can cause acute effects in the form of erythema through the inflammatory process. Antioxidants are substances that can protect the body from damage caused by ROS. Natural antioxidants can be found in vegetables and fruits, one of which comes from lemon extract (Citrus limon L.). Lemon extract is known to have active compounds in the form of flavonoids and phenols which can act as antioxidants. The aim of this research was to determine the protective effect of lemon extract on UVB exposure in the skin of male Wistar rats. Methods: This research used the true experimental posttest-only control group design method. Samples were divided into three treatment concentrations, namely ethanol extract of lemon 5 %, 10 %, and 20 %. Result: After testing for normality, the significance value was obtained (p < 0.05). Based on the results of the normality and homogeneity test, the results of the data distribution are not normal, and the homogeneous tests of the hypotheses used are the Kruskal-Wallis non-parametric test. Kruskal-Wallis’s non-parametric test results showed a significant difference in the significance value (p = 0.001). The best degree of erythema score was found in the cream of 10% ethanol extract of lemon with an average of 0.8 ± 0.84. Conclusion: The ethanol extract of lemon (Citrus limon L.) cream in a certain dosage has a significant effect on reducing the erythema degree score in the back skin of male Wistar rats (Rattus norvegicus) after exposure to UVB rays.