Maricha (Piper Nigrum)

Recent Research on Maricha (Piper nigrum)

• Choudhary, Prassan & Chakdar, Hillol & Singh, Dikchha & Selvaraj, Chandrabose & Singh, Sanjeev Kumar & Kumar, Sunil & Saxena, Anil. (2020). Computational Studies Reveal Piperine, the Predominant Oleoresin of Black Pepper (Piper nigrum) as a Potential Inhibitor of SARS- CoV- 2 (COVID- 19). Current science. 119. 1333- 1342. 10. 18520/ cs/ v119/ i8/ 1333- 1342. In this study, we screened 26 bioactive compounds present in various spices for activity against SARS- CoV- 2 using molecular docking. Results showed that piperine, present in black pepper, had a higher binding affinity (-7.0 kCal/ mol) than adenosine monophosphate (-6.4 kCal/ mol) towards the RNA-binding pocket of the nucleocapsid. Molecular dynamics simulation of the docked complexes confirmed the stability of piperine docked to nucleocapsid protein as a potential inhibitor of the RNA-binding site. Therefore, piperine seems to be a potential candidate to inhibit the packaging of RNA in the nucleocapsid and thereby inhibit viral proliferation. This study suggests that the consumption of black pepper may also help to combat SARS- CoV- 2 directly through possible antiviral effects, besides its immunomodulatory functions.
• Panda, Sunanda & Kar, Anand. (2003). Piperine Lowers the Serum Concentrations of Thyroid Hormones, Glucose, and Hepatic 5′ D Activity in Adult Male Mice. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 35. 523- 6. 10. 1055/ s-2003- 42652. Piperine, the main alkaloid of Piper nigrum fruits, was evaluated for its thyroid hormone and glucose regulatory efficacy in adult male Swiss albino mice. Its daily oral administration (2.50 mg/ kg) for 15 days lowered the serum levels of both the thyroid hormones, thyroxin (T (4)) and triiodothyronine (T (3)) as well as glucose concentrations with a concomitant decrease in hepatic 5′ D enzyme and glucose- 6- phosphatase (G- 6- Pase) activity. However, no significant alterations were observed in animals treated with 0.25 mg/ kg of piperine in any of the activities studied except an inhibition in serum T (3) concentration. The decrease in T (4), T (3) concentrations, and G- 6- Pase was comparable to that of a standard antithyroid drug, Propylthiouracil (PTU). The hepatic lipid-peroxidation (LPO) and the activity of endogenous antioxidants, superoxide dismutase (SOD), and catalase (CAT) were not significantly altered in either of the doses. It appears that the action of P. nigrum on thyroid functions is mediated through its active alkaloid, piperine. We also suggest that a higher dose of piperine may inhibit thyroid function and serum glucose concentration in euthyroid individuals.
• Liu, Yunbao & Yadav, Vivek & Aggarwal, Bharat & Nair, Muraleedharan. (2010). Inhibitory Effects of Black Pepper (Piper Nigrum) Extracts and Compounds on Human Tumor Cell Proliferation, Cyclooxygenase Enzymes, Lipid Peroxidation, and Nuclear Transcription Factor-kappa-B. Natural product communications. 5. 1253- 7. 10. 1177/ 1934578- X- 1000500822. Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Although hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anticancer and anti-inflammatory activities, whether black pepper and its active principle exhibit similar activities is not known. In this study, we have evaluated the antioxidant, anti-inflammatory, and anticancer activities of extracts and compounds from black pepper by using proinflammatory transcription factor NF- kappa- B, COX- 1 and -2 enzymes, human tumor cell proliferation, and lipid peroxidation (LPO). The capsaicinoids, the alkylamines, isolated from the hot pepper Scotch Bonnet were also used to compare the bioactivities of alkylamines and piperine from black pepper. All compounds derived from black pepper suppressed TNF-induced NF- kappaB activation, but alkyl amides, compound 4 from black pepper and 5 from hot pepper, were most effective. The human cancer cell proliferation inhibitory activities of piperine and alkyl amides in Capsicum and black pepper were dose-dependent. The inhibitory concentrations of 50% (IC 50) of the alkylamines were in the range of 13- 200 microg/ mL. The extracts of black pepper at 200 microg/mL and its compounds at 25 microg/mL inhibited LPO by 45- 85%, COX enzymes by 31- 80%, and cancer cell proliferation by 3.5-86.8%. Overall, these results suggest that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant, and anticancer activities.
• Singh, Ramnik & Rao, H. (2008). In vitro antioxidant activity of Piper nigrum Linn. Pharmacognosy Magazine. 4. 115- 120. The fractions R1, R2, and R3 obtained from pet ether extract of Piper nigrum Linn. (PEPN) were investigated for in vitro antioxidant activity. 1,1- Diphenyl- 2- picryl- hydrazyl ( DPPH) radical, superoxide anion radical, nitric oxide radical, and hydroxyl radical scavenging assays were performed. The free radical scavenging activity of the different fractions of PEPN increased in a concentration-dependent manner. R3 and R2 fractions of PEPN in 500 mu g/ml inhibited the peroxidation of a linoleic acid emulsion by 60.48 +/- 3.33% and 58.89 +/- 2.51%, respectively. In DPPH free radical scavenging assay, the activity of R3 and R2 was found almost similar. R3 (100 mu g/ml) fraction of PEPN inhibited 55.68 +/- 4.48% nitric oxide radicals generated from sodium nitroprusside whereas curcumin in the same amount inhibited 84.27 +/- 4.12%. Moreover, PEPN scavenged the superoxide radical generated by the Xanthine/Xanthine oxidase system. The fraction R2 and R3 in the dose of 1000 mu g/ml also inhibited 61.04 +/- 5.11% and 63.56 +/- 4.17% respectively, the hydroxyl radical generated by Fenton’s reaction. The amounts of total phenolic compounds were also determined, and 56.98 mu g pyrocatechol phenol equivalents were detected in one mg of R3.
• Gulcin, Ilhami. (2005). The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds. International journal of food sciences and nutrition. 56. 491- 9. 10. 1080/ 09637480- 500450248. Water and ethanol crude extracts from black pepper (Piper nigrum) were investigated for their antioxidant and radical scavenging activities in six different assays, namely, total antioxidant activity, reducing power, 1,1- Diphenyl- 2- picryl- hydrazyl (DPPH) free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Both water extract (WEBP) and ethanol extract (EEBP) of black pepper exhibited strong total antioxidant activity. The 75 microg/ ml concentration of WEBP and EEBP showed 95.5% and 93.3% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, at the same concentration, standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and alpha-tocopherol exhibited 92.1%, 95.0%, and 70.4% inhibition on peroxidation of linoleic acid emulsion, respectively. Also, total phenolic content in both WEBP and EEBP were determined as gallic acid equivalents. The total phenolics content of water and ethanol extracts was determined by the Folin-Ciocalteu procedure and 54.3 and 42.8 microg gallic acid equivalent of phenols was detected in 1 mg WEBP and EEBP.
• 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 increasing 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.
• Mishra, Raghav & Singh, Shio Kumar. (2009). Antispermatogenic and antifertility effects of fruits of Piper nigrum L. in mice. Indian Journal of experimental biology. 47. 706- 14. The effect of oral administration (25 and 100 mg/ kg body wt/ day, for 20 and 90 days) of fruit powder of Piper nigrum L. on the male reproductive organs of mice, Parkes strain, was investigated. Various reproductive endpoints such as organ weight, histopathology, sperm parameters, sialic acid and fructose contents, and fertility indices were assessed. Histologically, tests in treated mice, except in those treated with 100 mg of dose for 90 days, showed non-uniform degenerative changes in the seminiferous tubules, as both affected and normal tubules were observed in the same section. In mice treated with a 100 mg dose for 90 days, degenerative changes were observed in all the tubules. Affected seminiferous tubules showed intraepithelial vacuolation, loosening of germinal epithelium, the occurrence of giant cells, and mixing of spermatids of different stages of spermatogenesis; in severe cases, the tubules were lined by mainly a layer of Sertoli cells. The percentage of affected tubules in the testes of Piper-treated mice was dose-and duration-related. Further, Piper nigrum treatment for 20 days did not cause appreciable alterations in the histological appearance of the epididymis, while the treatment for 90 days caused detectable alterations in the duct. The treatment also had adverse effects on sperm parameters, levels of sialic acid and fructose, and litter size. Fifty-six days after cessation of treatment, the alterations induced in the reproductive organs recovered to control levels, though the litter size in females impregnated by Piper-treated males remained significantly decreased compared to controls.
• Akbar, Proity & Jahan, Ismet Ara & Hossain, Hemayet & Banik, Rajib & Nur, Husna & Hossain, Md. (2018). Antioxidant capacity of piper longum and piper nigrum fruits grown in Bangladesh. World Journal of Pharmaceutical Sciences. 2. 931- 941. The study is performed to determine and compare the antioxidant capacity of water and ethanol extracts of Piper longum and Piper nigrum fruits grown in Bangladesh. DPPH, ABTS and nitric oxide free radical scavenging activity, FRAP, superoxide dismutase, Fe 2+ ion chelating ability, total antioxidant capacity, reducing power assay, total flavonoid, and total phenolic content determination assays were used for evaluation of antioxidant capacity. The ethanol extracts of P. longum (long pepper from Dhaka, long pepper from Rajshahi) and P. nigrum (white pepper, black pepper) fruits showed significant activities compared to the water extracts in most of the antioxidant assays in a dose-dependent manner. The total phenolic and flavonoid contents ranged between 32.83 to 174.92 mg of GAE/g of dry extract and 33.44 to 172.98 mg of QE/g of dry extract, respectively. In total antioxidant capacity and FRAP assay, the activity of the extracts ranged from 9.05 to 199.17 mg AAE/g extract and 5.32 to 18.33 mg FeSO 4 E/g extract. In the DPPH scavenging and SOD assay, the percent inhibitions were found to be similar. However, ABTS, Fe 2+ scavenging, and reducing power assay showed better results for ethanol extracts, while nitric oxide scavenging activity showed better activity for water extracts.
• Alfauziah, Tazyinul. (2016). Production of Potential Antidiabetic Agent from Black Pepper (Piper nigrum) as Effort Enhancing National Resilience. Indonesia is one of the largest pepper manufacturers in the world, with either white or black pepper. Traditionally, black pepper is used for diarrhea, dyspepsia, cholera, and gastric ailments. It contains various active phytochemicals such as alkaloids, flavones, steroids, and terpenes. Piperine is the major alkaloid found in black pepper, about 4-6%. Recently, some research has shown that piperine is PPAR- agonist, a ligand-activated transcription factor in adipocytes and macrophages that increase adipocyte differentiation and insulin sensitivity. Therefore, piperine is a potential antidiabetic agent. This paper aims to propose an easy, efficient, and applicable extraction method of piperine from black pepper as an antidiabetic raw material. Various methods of extraction of piperine are soxhlet extraction, reflux extraction, maceration, and supercritical fluid extraction. Comparing those methods based on the piperine yield obtained, we found that the most suitable extraction method was maceration by glacial acetic acid, followed by partitioning with chloroform. The extract was dried on anhydrous sodium sulfate and then concentrated in a rotatory evaporator. Piperine is crystallized by diethyl ether. The Crystal of piperine obtained from this method was 4.6% with high purity. The high production level of black pepper in Indonesia can lead to piperine production as a raw material of antidiabetic agent independently. So, it can decrease the number of imported drugs’ raw materials and increase national resilience in the drug’s raw material provision, especially antidiabetic drugs.
• Godara, R. & Verma, M K & Katoch, Rajesh & Yadav, Anish & Dutt, Prabhu & Satti, Naresh & Katoch, Meenu. (2018). In vitro acaricidal activity of Piper nigrum and Piper longum fruit extracts and their active components against Rhipicephalus (Boophilus) microplus ticks. Experimental and Applied Acarology. 75. 10. 1007/ s10493- 018- 0268- 5. In vitro acaricidal activity of Piper nigrum and P. longum fruit extracts and their active components (piperine for P. nigrum and piperine and piper- longuminine for P. longum) was evaluated against adults engorged females of Rhipicephalus (Boophilus) microplus using adult immersion test. Three concentrations of each extract with four replications were used in the bioassay. Extracts significantly affected mortality rates of ticks in a dose-dependent manner ranged 12.5- 95.8 % for P. nigrum and 29.2- 87.5 % for P. longum, with an additional effect on the reproductive physiology of ticks by inhibiting oviposition (28.1- 96.9 % by P. nigrum and 36.1- 89.3 % by P. longum). However, the acaricidal and oviposition limiting properties were decreased significantly when the active component(s) of each extract was tested separately. However, the combination of piperine and piper longuminine (obtained from P. longum extract) caused 79.2 % mortality of ticks which is equivalent to the corresponding concentration (~ 5 %) of the extract. It can be concluded that the fruit extracts of P. nigrum and P. longum had both acaricidal and oviposition-limiting actions against the adults of R. (B.) microplus which could make it a valuable component of developing a sustainable strategy for integrated tick management.
• NAZISH, IRAM & SHAIKH, FAIZA & SAWANT, GAURANG. (2020). DOES A LOW DOSE OF PIPER NIGRUM EXTRACT EXERT ANTI-OBESITY ACTIVITY? International Journal of Pharmacy and Pharmaceutical Sciences. 41-46. 10.22159/ijpps.2020v12i5.27942. Objective: To evaluate the anti-obesity effect of aqueous P. nigrum extract in a murine model of high-fat diet (HFD) induced obesity. Methods: Male Wistar rats were fed with a high-fat diet (HFD) (20 g/ day/ rat) for a period of 50 d to induce obesity. Aqueous P. nigrum extract (20 mg/kg) was administered orally to high-fat diet (HFD) fed rats from the 8th day to the 50th day (total 42 d). The parameters like gain in body weight, serum lipids, insulin, and leptin were measured. Results: The rats treated with extract showed a significant reduction in body weight gain, serum insulin, leptin, and lipids as compared to rats fed with only a high-fat diet (HFD). In addition, the extract-treated group showed a considerable rise in high-density lipoprotein (HDL- C) level (29.61± 7.68 mg/ dl) as compared to the control group (23.23± 9.69 mg/ dl). Conclusion: The results indicate that aqueous P. nigrum extract possesses the potential to reduce obesity markers in high-fat diet (HFD) fed rats.
• Moraru, Aurelian & Roşca, Irina & Craciun, Bogdan & Nicolescu, Alina & Chiriac, Anca & Voicu, Victor. (2019). INSIGHTS OF THE ANTIMICROBIAL ACTIVITY OF PIPERINE EXTRACTED FROM PIPER NIGRUM L. FARMACIA. 67. 6. 10. 31925/Farmacia. 2019. 6. 24. this study aimed to present new insights into the antimicrobial activity of piperine extracted from Piper nigrum as compared to commercial piperine and to the activity of other similar compounds (namely: protocatechuic acid, L-ascorbic acid, L-tyrosine, and syringic acid) and in synergism with ampicillin and amphotericin B. For this, piperine was isolated, and purified and its structure and high purity were determined by NMR, FTIR, UV-Vis, and TLC analysis. A concentration of 100 mg/mL of piperine proved to have no cytotoxic effect on the opportunistic pathogens represented by Staphylococcus aureus and Escherichia coli and was slightly efficient against Candida albicans. Nevertheless, piperine improved the ampicillin activity against S. aureus by 14% and at the same time decreased the activity of amphotericin B against C. albicans by 54.2%, their antimicrobial properties being quite different compared to the commercial piperine.
• Vijayakumar, Ramasamy & Nalini, Namasivayamin. (2006). Piperine, an Active Principle from Piper Nigrum, Modulates Hormonal and Apolipoprotein Profiles in Hyperlipidemic Rats. Journal of Basic and clinical physiology and Pharmacology. 17. 71- 86. 10. 1515/ JBCPP. 2006. 17. 2. 71. To study the effect of piperine, an alkaloid, on thyroid hormones and apolipoproteins in high-fat-diet (HFD) and antithyroid drug-induced hyperlipidemic rats.
• Male Wistar rats were first divided into two groups, control diet and high-fat diet (HFD), and then subdivided into four subgroups of ten animals each. The animals were treated with the following regimens for 10 weeks: 1% carboxymethyl cellulose; 10 mg carbimazole (CM)/ kg body weight; 10 mg CM + 40 mg piperine/ kg body weight, and 10 mg CM + 2 mg atorvastatin /ATV/ kg body weight. Lipid profiles, hormone levels, and apolipoprotein levels were studied in all groups.
• HFD and/or CM administration significantly elevated the plasma levels of total cholesterol, VLDL, LDL, triglycerides, free fatty acids, and phospholipids, but significantly reduced the HDL levels. Moreover, CM administration significantly reduced apo A-I levels and T3, T4, and testosterone levels while significantly elevating plasma apo B, thyroid stimulating hormone (TSH), and insulin levels. The simultaneous administration of piperine and HFD significantly reduced plasma lipids and lipoproteins levels, except for HDL, which was significantly elevated. Piperine supplementation also improved the plasma levels of apo A-I, T3, T4, testosterone, and I and significantly reduced apo B, TSH, and insulin to near-normal levels.
• The data presented here provide evidence that piperine possesses thyrogenic activity, thus modulating apolipoprotein levels and insulin resistance in HFD-fed rats, opening a new view in the management of dyslipidemia by dietary supplementation with nutrients.
• Toma, Zainab. (2010). Antimicrobial Activity of Piperine purified from Piper nigrum. Alkaloid piperine was extracted from dry seeds of the plant Piper nigrum with ethanol by using soxhlet extraction then isolation and purification by recrystallization, the structure of Piperine was confirmed by the IR spectroscopy. The antimicrobial activity of Piperine was studied against gram+ve, gram-ve bacteria, and Candida albicans piperine showed potent antimicrobial activity against tested organisms especially C. albicans followed by E. coli and less than on P. aeruginosa the zone of inhibition ranges from 8- 23 mm and the minimum inhibitory concentrations (MIC) 3.125- 100 mg/ ml.
• Karthiga, Reshmi & Sathya, E. & Devi, P. Suganya. (2010). Isolation of piperidine from Piper nigrum and its antiproliferative activity. J. of Medicinal Plants Research. 4. 1535- 1546. Many plant-derived molecules have shown promising effects in therapeutics. Among the plants investigated to date, one showing enormous potential is the Piperaceae. The present study aimed to extract the phytochemical compounds in different solvent systems in Piper longum, Piper nigrum, and Piper cubeba as well as test their antibacterial and antitumor activity. HPTLC analysis of the P. nigrum sample showed six alkaloid bands; two alkaloid bands were similar to Piperine standards 1 and 2, the other alkaloid may be piperidine, piperettine, and piperanine. The P. longum sample contains three alkaloid bands: one band was similar to Piperine standard 1, the other may be Piper longumine and Piper longuminine and no alkaloid band was found in P. cubeba. The antibacterial activity was tested against gram-positive and negative organisms using the agar well diffusion method. High activity was found in P. nigrum ethanol extract against the organism Salmonella Typhii. The alkaloid piperidine was purified by refluxing method to check the antitumor activity which shows 51.38% of inhibition at 5μg/ml concentration that conforms the compound piperidine to be used as an anticancer drug for further mechanistic works.
• Kumari, P. Saravana & Priya, N.C. (2017). Antiviral activities and cytotoxicity assay of seed extracts of Piper longum and Piper nigrum on human cell lines. 42. 197- 202. Traditional plant-based compounds are seeking more attention from pharmaceutical companies to treat incurable diseases as they have no side effects, ease of recovery in large amounts, and high magnitude of activity. The present study deals with the anti-viral assay of methanolic and chloroform extract from seeds of Piper longum and Piper nigrum which are commonly used in food. From the seeds of Piper longum and Piper nigrum chloroform and methanolic extracts were collected by reflux method and extracts were evaluated against Vesicular stomatitis virus and human parainfluenza virus on HeLa cell lines. Cytotoxicity assay was carried out by MTT assay and LDH measurement. Anti-viral activity of Piper nigrum in chloroform extract showed higher activity than Piper nigrum in methanolic extract against Vesicular stomatitis Indiana virus and Human parainfluenza virus on the HeLa cell line. Piper longum in methanolic extract showed higher anti-viral activity than in chloroform extract against both viruses. Cytotoxicity assay of Piper longum treatment showed significant dose-dependent inhibition of growth of HeLa cells at IC 50 values of 46.24, 33.43, and 38.49 µg/ml at 24, 48, and 72 hours of incubation respectively. Similarly, the extract of Piper nigrum treatment also showed inhibition of the growth of HeLa cells at IC 50 values of 551.58, 24.18, and 17.47 µg/ ml at 24, 48, and 72 hours of incubation respectively. LDH measurement showed 100 % of inhibition at 260 mg/ml for both extracts of Piper nigrum. Piper longum in methanolic extract showed 100 % of inhibition at 240 mg/ml and no activity was observed in the case of chloroform extract. These results suggest that both Piper longum and Piper nigrum have significant anti-viral and anti-cancer activity in HeLa cells. HPTLC analysis of both the pepper in chloroform extract at 254 nm and 366 nm was done which produces different bands. At 254 nm resolutions of bands were poor and at 366 nm well-resolved bands with different intensity of color of bands confirmed the presence of piperidine.
• Karsha, P.V. & Lakshmi, O.B. (2010). Antibacterial activity of black pepper (Piper nigrum Linn.) with special reference to its mode of action on bacteria. Indian Journal of Natural Products and Resources. 1. 213- 215. During the present study, the antibacterial activity of black pepper (Piper nigrum Linn.) and its mode of action on bacteria was done. The extracts of black pepper were evaluated for antibacterial activity by the disc diffusion method. The minimum inhibitory concentration (MIC) was determined by the tube dilution method and the mode of action was studied on membrane leakage of UV 260 and UV 280 absorbing material spectrophotometrically. The diameter of the zone of inhibition against various Gram-positive and Gram-negative bacteria was measured. The MIC was found to be 50- 500 ppm. Black pepper altered the membrane permeability resulting in the leakage of the UV  260 and UV 280 absorbing material i.e., nucleic acids and proteins into the extracellular medium. The results indicate excellent inhibition of the growth of Gram-positive bacteria like Staphylococcus aureus, followed by Bacillus cereus and Streptococcus faecalis. Among the Gram-negative bacteria, Pseudomonas aeruginosa was more susceptible followed by Salmonella typhi and Escherichia coli.
• Akhtar, Mohd Sayeed & Birhanu, Guteta & Demisse, Shiferaw. (2014). Antimicrobial activity of Piper nigrum L. and Cassia didymobotyra L. leaf extract on selected food-borne pathogens. Asian Pacific Journal of Tropical Disease. 4. S911- S919. 10. 1016/ S2222- 1808 (14) 60757- X. Objective: To investigate the antimicrobial activity of leaf extract of Piper nigrum (P. nigrum) and Cassia didymobotyra (C. didymobotyra) (aqueous, methanol, ethanol and petroleum ether) against the foodborne pathogenic bacteria [Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Salmonella typhimurium and Pseudomonas aeruginosa)] and fungi [Aspergillus spp. and Candida albicans (C. albicans)] and also to investigate the presence of various phytochemicals in the leaf extracts of tested plants. Methods: The antimicrobial activity was determined by the disc diffusion method. Minimum inhibitory concentration (MIC), and minimum bactericidal and fungicidal concentration were determined by serial dilution method. Results: Methanol leaf extract of test plants exhibited greater antimicrobial activity against the selected bacterial and fungal strains. The MIC results showed that ethanol, methanol, and petroleum ether leaf extract of P. nigrum inhibited the growth of S. aureus and E. coli at a concentration of 12.5 mg/ mL. While ethanol and methanol leaf extracts of C. didymobotyra inhibited the growth of S. aureus at a concentration of 6.25 mg/ mL. The MIC values for ethanol, methanol, and petroleum ether leaf extract of P. nigrum inhibited the growth of C. albicans at a concentration of 25.0 mg/ mL. While it was reported that at a concentration of 12.5 mg/ mL methanol leaf extract of P. nigrum was against the Aspergillus spp. The MIC values of methanol leaf extract of C. didymobotyra inhibited the growth of C. albicans and Aspergillus spp. at a concentration of 12.5 mg/ mL and 6.25 mg/ mL, respectively. The minimum bactericidal concentration of ethanol, methanol leaf extract of P. nigrum for E. coli, and ethanol, methanol leaf extract of C. didymobotyra for S. aureus was recorded at a concentration of 12.5 mg/ mL. The minimum fungicidal concentration of ethanol and methanol leaf extract of P. nigrum and C. didymobotyra on C. albicans was recorded at a concentration of 25.0 mg/ mL, while, it was found at a concentration of 50.0 mg/ mL for petroleum ether and aqueous leaf extract of P. nigrum and C. didymobotyra. However, the MIC of methanol leaf extracts of P. nigrum and ethanol and methanol leaf extracts of P. nigrum and C. didymobotyra for Aspergillus spp. Was recorded at a concentration of 12.5 mg/mL, while, the MIC concentration ranged from 25.0- 50.0 mg/ mL for other tested solvent leaf extracts of P. nigrum and C. didymobotyra. Conclusions: This study suggests that test plants could be potential candidates for developing new antimicrobial drugs against the wide range of pathogenic bacteria and fungal strains.
• Nirwane, Abhijit & R., Bapat. (2012). The effect of methanolic extract of Piper nigrum fruits in Ethanol-CCl4 induced hepatotoxicity in Wistar rats. Der Pharmacia Lettre. 4. Piper nigrum popularly known as ‘Black Pepper’ contains an abundant amount of piperine alkaloids. Piperine alkaloids have been implicated in Hepatoprotective activity. To evaluate the effect of methanolic extract of Piper nigrum fruits in Ethanol- CCl 4 induced hepatotoxicityWistar rats. The methanolic extract of P. nigrum (MEPN) (100 and 200 mg/ kg, p.o., 15 days) and Piperine (PPR) (50 mg/ kg, p.o., 15 days) was gavaged daily to the rats along with Ethanol [40%, 2ml/ 100gm, p.o. for 15 days, twice a day] & on 14th Day CCL 4 [1:1 in groundnut oil, 0.1 ml/ kg, s.c.]. The levels of Triglycerides (TG), aminotransferases (AST, ALT), alkaline phosphatase (ALP), Bilirubin and Superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GSH) and Lipid peroxidation (TBARS) levels in liver were measured. Morphological and histopathological indices in the liver of healthy and Ethanol-CCl4 treated rats were also measured. In the underlying study, Ethanol- CCl4 exhibited an increase in the hepatic biomarkers (TG, AST, ALT, ALP, and Bilirubin), LPO which were significantly decreased after pretreatment with MEPN (100, 200 mg/kg), and PPR (50 mg/kg). Ethanol- CCl4 significantly decreased levels of SOD, CAT, and GSH which were restored with MEPN and PPR. The results were similar to that of Liv52 [1ml/ kg, p.o. for 15 days], which served as a reference standard. Histopathological studies were also in agreement with the above. The study indicates that P. nigrum possesses potential hepatoprotective activity which may be attributed to its piperine alkaloids, having therapeutic potential in the treatment of liver disorders.
• Tasleem, Farhana & Azhar, Iqbal & Ali, Syed & Perveen, Shaista & Mahmood, Zafar. (2014). Analgesic and anti-inflammatory activities of Piper nigrum L. Asian Pacific Journal of tropical medicine. 7S1. S461- 8. 10. 1016/ S1995-7645 (14) 60275- 3. Objective:  To evaluate and compare the analgesic and anti-inflammatory activity of the pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. Methods:  The analgesic activity was determined by tail immersion method, analgesia meter, hot plate, and acetic acid-induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Results:  Piperine at a dose of 5 mg/ kg and ethanol extract at a dose of 15 mg/ kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P< 0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/ kg using analgesia-meter in rats. However, with the hotplate method, piperine produced significant (P< 0.05) analgesic activity at lower doses (5 and 10 mg/ kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in the writhing test, ethanol extract significantly (P< 0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/ kg completely terminated the writhes in mice. In the evaluation of the anti-inflammatory effect using a plethysmometer, piperine at doses of 10 and 15 mg/kg started producing an anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. Conclusions:  It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.
• Shamkuwar, P.B. & Agrawal, Y.P. & Chavan, Shital. (2013). Evaluation of active constituents of Piper nigrum in diarrhea. Der Pharmacia Lettre. 5. 121-125. Piperine was extracted and isolated from Piper nigrum. The antidiarrhoeal effect of piperine and aqueous extract of Piper nigrum was examined in castor oil and magnesium sulfate-induced diarrhea in mice. Piperine has shown significant inhibition of diarrhea when compared with the anti-diarrheal effect of aqueous extract of Piper nigrum. The results indicate that piperine is the active anti-diarrhoeal constituent of Piper nigrum.
• Ghosh, Sourav & Kumar, Arvind & Sachan, Dr. Neetu & Chandra, Phool. (2021). Anxiolytic and antidepressant-like effects of essential oil from the fruits of Piper nigrum Linn. (Black pepper) in mice: involvement of serotonergic but not GABAergic transmission system. Heliyon. 7. e06884. 10. 1016/ j. heliyon. 2021.  e06884. In this study, the anxiolytic activity of Piper nigrum essential oil (PNEO) was evaluated in the elevated plus maze (EPM) and the antidepressant-like effect was evaluated through a tail suspension test (TST) in mice. Flumazenil, a competitive inhibitor of the GABA receptor in the benzodiazepine site, and WAY-100635 maleate salt, a 5- HT1A receptor antagonist were used to find out the possible mechanism(s) of action of PNEO. To exclude the false-positive results due to the enhancement of the locomotor activity, the animals were submitted to an open field test (OFT). We also measured monoamine levels in the mice’s brains after acute PNEO treatment. The data obtained from the study suggest that the anxiolytics and antidepressant-like effect of PNEO have been observed in EPM and TST respectively in a dose-dependent manner after oral acute and repetitive treatment. WAY- 100635, but not flumazenil was able to reverse the effect of PNEO in EPM and TST both, indicating the possible involvement of the 5- HT1A receptor. The neurochemical analysis showed no alteration in monoamine levels in mice brains. Furthermore, no locomotor impairment or sign of toxicity or changes in body weight, or abnormalities in the biochemical parameters, except for a significant decrease in total cholesterol level was observed after treatment with PNEO. The findings suggest that Piper nigrum EO possesses a dual anxiolytic and antidepressant-like effect through the possible involvement of serotonergic transmission.
• Panda, Sunanda & Kar, Anand. (2003). Piperine Lowers the Serum Concentrations of Thyroid Hormones, Glucose and Hepatic 5′D Activity in Adult Male Mice. Hormone and metabolic research Hormones et metabolism. 35. 523- 6. 10. 1055/ s-2003- 42652. Piperine, the main alkaloid of Piper nigrum fruits, was evaluated for its thyroid hormone and glucose regulatory efficacy in adult male Swiss albino mice. Its daily oral administration (2.50 mg/ kg) for 15 days lowered the serum levels of both the thyroid hormones, thyroxin (T (4)) and triiodothyronine (T (3)) as well as glucose concentrations with a concomitant decrease in hepatic 5′ D enzyme and glucose- 6- phosphatase (G- 6- Pase) activity. However, no significant alterations were observed in animals treated with 0.25 mg/ kg of piperine in any of the activities studied except an inhibition in serum T (3) concentration. The decrease in T (4), T (3) concentrations, and G- 6- Pase was comparable to that of a standard antithyroid drug, Propylthiouracil (PTU). The hepatic lipid-peroxidation (LPO) and the activity of endogenous antioxidants, superoxide dismutase (SOD), and catalase (CAT) were not significantly altered in either of the doses. It appears that the action of P. nigrum on thyroid functions is mediated through its active alkaloid, piperine. We also suggest that a higher dose of piperine may inhibit thyroid function and serum glucose concentration in euthyroid individuals.