Pippali (Piper Longum)

Recent Research on Piper longum

• Ramadas, Dr Dinesha & D, Chikkanna. (2014). ANTIOXIDANT ACTIVITIES OF PIPPALI (PIPER LONGUM) PROTEINS. International Journal of Pharmaceutics and Drug Analysis. 2. 811- 814. The study was conducted to find and evaluate the antioxidant activities of proteins isolated from boiling water extract of Pippali (Piper longum) (long pepper). The antioxidant activity of the proteins was analyzed using Hydroxyl radical scavenging assay and lipid peroxidation inhibition assays. The proteins were analyzed for their thermal stability. Cytotoxic studies showed that the proteins are non-toxic. The results obtained are promising when compared with standard antioxidants Vitamin E, BHA, and Ascorbic acid.
• Xavier, Jobi & Thomas, Seju. (2020). Antioxidant Activities of Leaves and Fruits of Piper nigrum and Piper longum. Asian Journal of Plant Sciences. 19. 127- 132. 10. 3923/ ajps. 2020. 127. 132. Background and Objectives: Herbs and spices have been used to enhance the flavors of food, as well as for their medicinal purposes. Herbs usually contain antioxidant properties. The present study focused on the importance of the antioxidants present in Piper nigrum and Piper longum widely used by the people of India in their food. Materials and Methods: The methanolic extracts of the leaves and fruits of both Piper nigrum and Piper longum were prepared using the soxhlet extraction method. The total phenolic content (TPC) of the plant samples was determined by the Folin-Ciocalteu method. The total flavonoid content (TFC) of the plant was determined. The inhibitory effect of the plant against oxidation by peroxides was evaluated by ferric thiocyanate assay. Results: The highest concentration of phenol was obtained from Piper nigrum leaves. The highest flavonoid content was observed in the Piper nigrum leaves (0.15 mg). The higher reducing potency of the antioxidants was present in the leaves and fruit of Piper nigrum and Piper longum exhibiting their antioxidant properties. The ability of the plant extracts of Piper nigrum and Piper longum against lipid peroxidation was revealed through the efficiency of inhibiting the radicals at a percentage of 58.33, 77.77, 66.66, and 22.22, respectively. Conclusion: From the study, it was concluded that the leaves and fruits of Piper nigrum and Piper longum have shown high antioxidant properties. So, they are considered to be rich sources of natural antioxidants for the food, cosmetic, and pharmaceutical industries.
• Archana, D. & Dixitha, M. & Santhy, K. (2015). Antioxidant and anti-clastogenic potential of Piper longum L. International Journal of Applied Pharmaceutics. 7. 11- 14. Objective: The present study aimed to evaluate the antioxidant and anti-clastogenic potential of the methanol extract of Piper longum L (MEPL). Methods: Chromatographic analysis was carried out using thermo GC-Trace Ultra Ver: 5.0 GC-MS. Antioxidant activities were assessed by DPPH free radical scavenging assay and reducing power assay. Based on the antioxidant activity, micronuclei formation in peripheral blood lymphocytes was analyzed. The protection afforded by Piper longum L. against the cytotoxicity of peripheral blood lymphocytes was confirmed by the micronucleus (MN) assay. Results: The GC- MS analysis provides different peaks determining the presence of eighteen phytochemical compounds with different therapeutic activities. The methanol extract at a concentration of 40 μg/ ml showed the highest antioxidant activity by DPPH assay (68.42 %) comparable to standard ascorbic acid (73.68 %). The reducing power observed was in the order of 40 μg/ ml > 20 μg/ ml> 10 μg/ ml. MEPL treatment decreased the frequency of MN in a concentration-dependent manner. Conclusion: A substantial number of bioactive components are present in Piper longum L. A good correlation of the antioxidant capacity of the plant was established by different assay methodologies. MN test confirmed the anti-clastogenic potential in peripheral blood lymphocytes. 
• Akbar, Proity. (2014). 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, Fe2+ 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 FeSO4 E/ g extract. In the DPPH scavenging and SOD assay, the percentage inhibitions were found to be similar. However, ABTS, Fe2+ scavenging, and reducing power assay showed better results for ethanol extracts, while nitric oxide scavenging activity showed better activity for water extracts.
• Kumari, Mamta & Bk, Ashok & Ravishankar, Basavaiah & Pandya, Tarulata & Acharya, Rabinarayan. (2012). Anti-inflammatory activity of two varieties of Pippali (Piper longum Linn.). Ayu. 33.  307- 10. 10. 4103/ 0974- 8520. 105258. The present study has been undertaken to evaluate the anti-inflammatory activity of two varieties of Pippali in acute and sub-acute experimental models of inflammation in albino rats. Four different market samples of each variety of Pippali were procured from different regions of India. The samples collected from South India which have given more extractive values were selected for screening for anti-inflammatory activity. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 200 mg/ kg and the activity was compared with standard anti-inflammatory drugs in both models. Among the two different test samples studied, it was found that the Chhoti variety of Pippali suppressed inflammation of both acute and sub-acute phases, while the Badi variety of Pippali only of the acute phase. Thus, for therapeutic utility, the Chhoti variety of Pippali may be considered over the Badi variety.
• Guo, Ziyan & Xu, Jie & Xia, Jianhua & Wu, Zi & Lei, Jiachuan & Yu, Jianqing. (2019). Anti-inflammatory and anti-tumor activity of various extracts and compounds from the fruits of Piper longum L. Journal of Pharmacy and Pharmacology. 71. 10. 1111/ jphp. 13099. Objectives- To explore effective extraction methods and to find active constituents, we investigated the biological activity of three extracts and isolated active compounds from the fruits of Piper longum L. Three extracts from the fruits were obtained by reflux, ultrasonic, and supercritical fluid extraction, respectively. Active compounds were isolated by the bioassay‐guided method. The anti‐inflammatory activity, antiproliferation activity, and cytotoxicity were evaluated. The apoptosis was detected by the Hoechst 33258 staining assay. The relevant proteins were investigated by Western blot assay. The anti‐inflammatory activity and cytotoxicity of supercritical fluid extract (SE) were stronger than those of the other two extracts. Among all isolated compounds, the anti‐inflammatory activity of eight compounds was stronger than that of indomethacin, and compounds 8, 9, 11, 14, and 15 were found to possess anti‐inflammatory effects for the first time. Compounds 1, 2, 3, and 14 exhibited significant cytotoxicity against cancer cells. SE and piperine were found to reduce colony formation, inhibit cell migration, and promote apoptosis through increasing cleaved PARP and the ratio of Bax/ Bcl‐2. Conclusions- The anti‐inflammatory and antitumor effects of SE were better than those of the other two extracts. The compounds responsible for the activity were elucidated. SE and piperine inhibit cell growth through apoptosis.
• Bhitre, M.J. & Fulmali, Sushma & Kataria, Maya & Anwikar, Shraddha & Kadri, Harsha. (2008). Antiinflammatory activity of the fruits of Piper longum Linn. Asian Journal of Chemistry. 20. 4357- 4360. Inflammation is a response of vascularized living tissue to the local injury. It is the body’s defense mechanism, which is closely intertwined with the process of repair. It serves to destroy or dilute the injurious agents and also reconstitute the damaged tissue by regeneration. The severe side effects of steroidal and non-steroidal anti-inflammatory drugs evoked us to search for new anti-inflammatory drugs from indigenous sources. The methanolic, ethanolic, chloroform, ethyl acetate, and pet ether extracts of fruits of Piper longum Linn were tested to study the anti-inflammatory activity using the technique of carrageenan-induced paw edema in albino rats. The extract showed significant anti-inflammatory activity comparable to the reference standard aspirin.
• Kumar, Ashok & Panghal, S & Mallapur, S & Kumar, M & Ram, Veerma & Singh, B. (2009). Anti Inflammatory Activity of Piper longum Fruit Oil. Indian journal of pharmaceutical sciences. 71. 454- 6. 10. 4103/ 0250- 474X. 57300. In the present study, anti- anti-inflammatory activity of the Piper longum dried fruit oil was studied in rats using the carrageenan-induced right hind paw edema method. The activity was compared with that of standard drug ibuprofen. The dried fruit’s oil inhibited carrageenan-induced rat paw edema. The results indicated that the dried fruit oil produced significant (p< 0.001) anti- inflammatory activity when compared with the standard and untreated control.
• Sunila, E & Kuttan, G. (2004). Immunomodulatory and Antitumor activity of Piper longum Linn and Piperine. Journal of Ethnopharmacology. 90. 339-46. 10. 1016/ j. jep. 2003. 10. 016. The alcoholic extract of the fruits of the plant Piper longum and its component piperine were studied for their immunomodulatory and antitumor activity. The alcoholic extract of the fruits was 100 % toxic at a concentration of 500 microg/ ml to Dalton’s lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ ml. Alcoholic extract and piperine were also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/ dose/ animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8 %, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9 %, respectively, in Balb/c mice. The number of plaque-forming cells was also enhanced significantly by the administration of the extract (100.3 %) and piperine (71.4 %) on the 5th day after immunization. Bone marrow cellularity and alpha-esterase-positive cells were also increased by the administration of Piper longum extract and piperine.
• Jalalpure, Sunil & Patil, M.B. & Prakash, N.S. & Hemalata, K. & Manvi, F. V. (2003). Hepatoprotective activity of fruits of Piper longum L. Indian Journal of Pharmaceutical Sciences. 65. 363- 366. Ethanol extracted from Piper longum fruits and five different crude fractions, petroleum ether (40- 60 %), solvent ether, ethyl acetate, butanol, and butanone were subjected to preliminary qualitative chemical investigations. The ethanolic extract and all other fractions were screened orally for hepatoprotective activity in adult Wistar rats. The ethanolic extract and butanol fraction have shown significant activity, lowering the serum enzymes glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in rats treated with carbon tetrachloride when compared to control and Liv- 52- treated rats.
• Wakade, Alok & Shah, Abhishek & Kulkarni, Mp & Juvekar, Archana. (2008). Protective effect of Piper longum L. on oxidative stress-induced injury and cellular abnormality in adriamycin-induced cardiotoxicity in rats. Indian journal of experimental biology. 46. 528- 33. The effect of methanolic extract of fruits of P. longum (PLM) on the biochemical changes, tissue peroxidative damage, and abnormal antioxidant levels in adriamycin (ADR) induced cardiotoxicity in Wistar rats was investigated. PLM was administered to Wistar albino rats in two different doses, by gastric gavage (250 mg/ kg and 500 mg/ kg) for 21 days followed by ip ADR (15 mg/ kg) on the 21st day. ADR administration showed a significant decrease in the activities of marker enzymes aspartate transaminase, alanine transaminase, lactate dehydrogenase, and creatine kinase in the heart with a concomitant increase in their activities in serum. A significant increase in lipid peroxide levels in the heart of ADR-treated rats was also observed. Pretreatment with PLM ameliorated the effect of ADR on lipid peroxide formation and restored the activities of marker enzymes. Activities of myocardial antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase along with reduced glutathione were significantly lowered due to cardiotoxicity in rats administered with ADR. PLM pretreatment augmented these endogenous antioxidants. Histopathological studies of the heart revealed degenerative changes and cellular infiltrations in rats administered with ADR and pretreatment with PLM reduced the intensity of such lesions. The results indicate that PLM administration offers significant protection against ADR-induced oxidative stress and reduces cardiotoxicity by virtue of its antioxidant activity.
• Sunila, E.S. & Kuttan, G. (2006). Protective effect of Piper longum fruit ethanolic extract on radiation-induced damages in mice: A preliminary study. Fitoterapia. 76. 649- 55. 10. 1016/ j. fitote. 2005. 08. 008. The radioprotective property of an ethanolic extract of Piper longum fruits (EEPLF) was investigated in Swiss mice. The white blood cell (WBC) count in irradiated control mice was drastically reduced to 1900 cells/ mm3 on the third day but in treated animals the count was 2783.3 cells/ mm3. The number of bone marrow cells and alpha-esterase positive cells was also enhanced by the EEPLF administration (16.7 x 10 (6) cells/ femur and 946.5/ 4000 cells, respectively) when compared to the radiation-exposed control animals (12.2 x 10 (6) cells/ femur and 693.5/ 4000 cells, respectively). EEPLF reduced the elevated levels of glutathione pyruvate transaminase (GPT), alkaline phosphatase (ALP), and lipid peroxidation (LPO) in the liver and serum of radiation-treated animals. The extract administration also increased the reduced glutathione (GSH) production to offer radioprotection.
• Khan, Mohammad & Imran, Shaikh & Khan, Mobashshera. (2021). Effects of Herbal Formulations in Management of Uterine Fibroid (Sulah- E- Rehm) – A Case Report. International Journal of AYUSH Case Reports. 5. 91- 97. 10. 52482/ ijacare. v5i2. 221. Uterine fibroid is the most common benign and solid tumor in females during reproductive life. Approximately 15- 25 million Indian women have been affected by fibroid uterus. Histologically it is composed of smooth muscle and fibrous connective tissue of varying proportions. It is considered as Sulah (tumor) in Unani classic literature, as Alibn- e- Abbas Majusi (930- 994 AD) defined it under the topic of Warm-e-Balghami; as it is a swelling filled with viscid phlegm (Balgham- e- Ghaleez). The present paper deals with reports of a 30 year old female having uterine fibroids measuring 2.6 cm× 3.1 cm, 2.6 cm× 3.6 cm, with a left ovarian cyst of 3.1 cm × 4 cm. Patient was treated with herbal formulations; Majun Dabeedul Ward (5 gm paste), Kanchanar Guggul (2 tablets) and Niswani (10 ml syrup) twice a day for 8 consecutive weeks as oral administration. The patient was clinically assessed fortnightly, and radiologically just after treatment. Patients have shown encouraging results in the post-treatment investigation of Ultrasonography and finally, patients got free from uterine fibroids without operation. The drugs were found to be safe and effective in this case.
• Yamada, Noriko & Nishihara, Chie & Yoshimura, Hiroyuki & Yamaguchi, Yasunaga & Takagaki, Ryoji & Miyakoshi, Masazumi & Mizutani, Kenji. (2009). Effects of Piper longum L. on chills in Japanese young women: Time-dependent changes in skin surface temperature and its recovery rate following the exposure to mild cold stress. Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology. 29. 7- 15. Chills can lead to problems such as insomnia, mental fatigue, and unstable emotions. Increasing evidence shows that young women, as well as menopausal women, suffer from chills. The present study investigated the effect of Piper longum L. on chills in young women. Participants with (n = 16) and without (n = 16) chills were sampled randomly from female university students using reported discriminative criteria (Yamada et al, 2007). Each participant was randomly assigned to low- (15 mg) and high-dose (30 mg) P. longum groups. We determined the severity of complaints related to chills, physical parameters (body mass index, body fat ratio, and blood pressure), the peripheral circulation dynamics using a laser tissue blood flow meter, and the skin surface temperature in the fingers using a thermograph. Mild cold stress was applied 10 min after taking a capsule containing P. longum or a dextrin placebo. Then, a thermograph was recorded every minute for 11 min. Piper longum significantly facilitated the recovery of skin surface temperature at either low or high dosages in participants with chills. In subjects without chills, neither high- nor low-dosage of P. longum had an effect. Our findings have important implications for the utility of P. longum in women with chills.
• Whitehouse, Scott & Chen, Pei-Lin & Greenshields, Anna & Nightingale, Mat & Hoskin, David & Bedard, Karen. (2016). Resveratrol, piperine, and apigenin differ in their NADPH-oxidase inhibitory and reactive oxygen species-scavenging properties. Phytomedicine. 23. 10. 1016/ j. phymed. 2016. 08. 011. Many plant-derived chemicals have been studied for their potential benefits in ailments including inflammation, cancer, neurodegeneration, and cardiovascular disease. The health benefits of phytochemicals are often attributed to the targeting of reactive oxygen species (ROS). However, it is not always clear whether these agents act directly as antioxidants to remove ROS, or whether they act indirectly by blocking ROS production by enzymes such as NADPH oxidase (NOX) enzymes, or by influencing the expression of cellular pro- and antioxidants. Hypothesis/Purpose:  Here we evaluate the pro- and antioxidant and NOX -NOXinhibiting qualities of four phytochemicals: celastrol, resveratrol, apigenin, and piperine. Study design: This work was done using the H661 cell line expressing little or no NOX, modified H661 cells expressing NOX1 and its subunits, and an EBV- transformed B-lymphoblastoid cell line expressing endogenous NOX2. ROS was measured using Amplex Red and nitroblue tetrazolium assays. In addition, direct ROS scavenging of hydrogen peroxide or superoxide generated was measured using Amplex Red and methyl cypridina luciferin analog (MCLA). Results: Of the four plant-derived compounds evaluated, only celastrol displayed NOX inhibitory activities, while celastrol and resveratrol both displayed ROS scavenging activity. Very little impact on ROS was observed with apigenin or piperine. The results of this study reveal the differences that exist between cell-free and intracellular pro-oxidant and antioxidant activities of several plant-derived compounds.
• Kaushik, Pawan & Kaushik, Dhirender & Rani, Ruby & Sacher, Disha & Yadav, Jyoti. (2012). In vivo and in vitro Antiasthmatic Studies of Plant Piper longum Linn. International Journal of Pharmacology. 8. :192- 197. 10. 3923/ ijp. 2012. 192. 197. The fruits of Piper longum Linn, are used in allergic skin disorders and asthma. The effect of petroleum ether, alcoholic, and decoction of the fruits of P. longum was studied for antihistaminic activity using Guinea pig ileum preparation (in vitro), histamine-induced bronchospasm in Guinea pigs, and haloperidol-induced catalepsy in mice (in vivo). Its anti-allergic activity was evaluated using milk-induced leukocytosis in mice and passive paw anaphylaxis in rats (in vivo). The extracts (100 μg mL -1) significantly (p< 0.01) inhibited the histamine-induced contraction of isolated Guinea-pig ileum preparation. The extracts (50, 100, 200 mg kg -1) showed significant (p< 0.01) activity, and an increase in the dose of extract increased the % protection in histamine-induced bronchospasm and also showed significant (p< 0.01) activity in haloperidol-induced catalepsy and passive paw anaphylaxis. In milk-induced leukocytes, petroleum ether and decoction extract (200 mg kg -1) showed a significant (p<0.05) decrease in the number of leukocytes and alcoholic extract didn’t show any significant effect.
• Nabi, Shaik & Kasetti, Ramesh & sirasanagandla, Swapna & Tilak, Thandaiah & Jyothi kumar, DR Malaka Venkateshwarulu & Apparao, Chippada. (2013). Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats. BMC complementary and alternative medicine. 13. 37. 10. 1186/ 1472- 6882- 13-37. The available drugs for diabetes, Insulin, or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats.
• Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/ kg. b. w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using a Student t-test and one-way analysis (ANOVA) followed by DMRT. During the short-term study, the aqueous extract was at a dosage of 200 mg/ kg. b. w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ-induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic-treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic properties. From the above results, it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ-induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti-hypoglycemic agents.
• Sutrakar, Suresh. (2015). Dyslipidemic and Antioxidant activity of Piper longum extract in hyperlipidemic rats. Research Journal of Pharmacy and Technology. 8. 1609. 10. 5958/ 0974- 360X. 2015. 00288.7. The dyslipidemic and antioxidant activity of Piper longum extract has been studied in triton and high-fat diet-fed hyperlipidemic rats. The extract lowered the serum lipids at (200 mg/ kg, b. w., p. o.) in triton WR- 1339 induced hyperlipidemia. Chronic feeding of this extract (100 mg/ kg, b.w.) in animals simultaneously fed with a high-fat diet (HFD) for 30 days caused a lowering of lipid and apoproteins levels of lipoproteins in experimental animals. P. langum activates lipolytic enzymes in plasma and liver lipids. These extracts increased fecal bile acid extraction and enhanced plasma lecithin: cholesterol acyltransferase activity. Piper longum extract showed potent inhibition of antioxidants and scavengers of oxygen free radical activity (in vitro) and it induced oxidative stress.
• Soni, Gaurav & Verma, T. (2013). Antihyperlipidemic activity of seed extract of Piper attenuatum in triton X- 100 induced hyperlipidemia in rats. Journal of Chemical and Pharmaceutical Research. 5. 1370- 1373. Piper attenuatum is a potent medicinal plant in the Indian systems of medicine. Piper attenuated has Piperine, Piperlonguminine, and other active constituents which are used as muscle relaxants, central nervous system depressants, in headaches, and as insecticide agents against Musca domestica. Piperine reduces the total body temperature and displays analgesic, and anti-inflammatory activities. The present study aims to determine the Antihyperlipidemic activity of the Ethanolic seed extract of plant Piper attenuatum (Linn.) B. Ham. (Fam. Piperaceae). Piperine was the first amide to be isolated from Piper species. Ethanolic extracts of Piper attenuatum with a dose of 200 mg/ kg exhibited significant Anti-Hyperlipidemic activity in Triton X- 100 Induced Hyperlipidemia in rats (P< .05). It was found that Piperine & Piperlonguminine the active constituent of the plant was responsible for the Anti- Hyperlipidemic activity because this constituent can reduce the Total Cholesterol & Total Triglyceride level in rats. Fenofibrate was used as a standard drug (65 mg/ kg). The total period of this study was one week.
• Shanmugam, Manoharan & Silvan, Simon & Krishnamoorthi, Vasudevan & Subramanian, Balakrishnan. (2007). Antihyperglycemic and Antilipidperoxidative Effects of Piper longum (Linn.). Dried Fruits in Alloxan Induced Diabetic Rat. Journal of Biological Sciences. 7. 10. 3923/ jbs. 2007. 161. 168. Piper longum (Piperaceae family) is used in Indian traditional medicine as a remedy for various disorders including diabetes mellitus. The aim of the present study was to investigate the antihyperglycemic and anti-lipid peroxidative effects of ethanolic extract of Piper longum dried fruits (PLEFet) in alloxan-induced diabetic rats. Diabetes mellitus was induced in overnight fasted (12 h) Wistar rats by a single intraperitoneal injection of a freshly prepared solution of alloxan monohydrate (150 mg/ kg) in physiological saline. The blood glucose level, carbohydrate metabolizing enzymes, and the status of lipid peroxidation and antioxidants were assayed using specific colorimetric methods. Oral administration of PLEFet has shown significant anti-hyperglycemic, anti-lipid peroxidative, and antioxidant effects in diabetic rats. PLEFet also corrected the metabolic alterations observed by the activities of several carbohydrate metabolizing enzymes (hexokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, fructose 1.6-bisphosphatase, and glycogen phosphorylase) in alloxan-induced diabetic rats. The antihyperglycemic effect of PLEF is comparable to that of the standard reference drug, glibenclamide. Present results indicate that PLEFet has potent antihyperglycemic and anti-lipid-peroxidative effects in alloxan-induced diabetic rats. PLEFet can therefore be used as an alternative remedy for diabetes and oxidative stress-associated diabetic complications.
• Bi, Ying & Qu, Peng-Cheng & Wang, Qing-Song & Zheng, Li & Liu, Hao-Long & Luo, Rong & Chen, Xiao-Qing & Ba, Yin-Ying & Wu, Xia & Yang, Hui. (2015). Neuroprotective effects of alkaloids from Piper longum in an MPTP- induced mouse model of Parkinson’s disease. Pharmaceutical biology. 53. 1516- 24. 10. 3109/ 13880209. 2014. 991835. Context:  Alkaloids of Piper longum L. (Piperaceae) (PLA) include piperine and piperlonguminine. Piper longum and piperine have multiple biological properties including antioxidant activity. Objective:  The present study investigated the neuroprotective effects of PLA in an MPTP-induced mouse model of Parkinson’s disease. Materials and methods: PLA was prepared by extracting the dry seed of P. longum using 85 % ethanol. Adult male C57BL/ 6 mice were divided into eight groups of 12 rats each. Experimental and control groups received an equivalent volume of saline, 0.5 % CMC- Na, and 0.1 % Tween 80, treated groups received oral PLA (30, 60, and 120 mg/ kg), other groups treated with piperine (60 mg/ kg) or Madopar (50 mg/ kg). The PLA prevention group (PLA- Pr) administrated PLA (120 mg/ kg) for 1 week before the MPTP challenge. Except for the PLA- Pr group, others were treated for seven consecutive weeks. Parkinson’s disease was induced by injecting MPTP intraperitoneally (25 mg/ kg) twice weekly for five consecutive weeks. Dopaminergic (DA) neurons and their metabolism were detected by UFLC-MS/MS. Tyrosine hydroxylase (TH)-immunohistochemistry assay and Western blotting were performed. The antioxidant enzymatic levels were determined by kit-based assays. Results: The LD50 value of PLA was determined at 1509 mg/ kg of body weight. PLA (60 mg/ kg) can significantly increase total movement time and distance (p < 0.05), increase levels of DA (p < 0.05) and DOPAC (p < .05), increase glutathione (GSH) level and superoxide dismutase (SOD) activity (p < 0.05), and decrease the lipid peroxidation of malondialdehyde (MDA) (p < 0.05) in PLA-treated groups as compared with the control group. Discussion and conclusion:  Our results indicate that PLA possesses neuroprotective effects and has ameliorative properties in dopaminergic neurons.
• Subramanian, Umadevi & Poongavanam, Sharmila & Vanisree, AJ. (2009). Studies on the neuroprotective role of Piper longum in C6 glioma-induced rats. Investigational new drugs. 28. 615- 23. 10. 1007/ s10637- 009- 9301- 1. Many naturally occurring substances of plant origin ingested in the human diet exhibit anticarcinogenic and antimutagenic effects. One of the active phytochemicals that shows an active anticarcinogenic role is Piper longum Linn. (Pl). Pl is widely used in the Ayurvedic industry due to its property in healing some of the bodily ailments. Despite being known for its antioxidant, antimicrobial, and anticarcinogenic effects, its relation to the brain and its tumor development is still scarce. Hence, the experimental glioma model was developed in rats using C6 glioma cells and the effect of Pl was evaluated in the brain tissue of the experimental group of rats. From the study, the glioma-induced animals showed an increased level of lipid peroxides (LPO), tissue marker enzymes lactate dehydrogenase (LDH), creatine kinase (CK), 5’nucleotidase (5’ND), and acetylcholine esterase (AChE). But Pl treatment (20 mg/ kg body weight) significantly attenuated these alterations thereby showing a potent anticancer effect in glioma-induced rats. In addition, the anticarcinogenic effect of Pl was confirmed by microscopic analysis and the restoration of increased lipids and protein-bound carbohydrates (PBCs) in the brain tissue of glioma-induced rats. Hence our results implicate a major role for Pl in preventing cancer development in the experimental glioma model.
• Wang, Hao & Liu, Jia & Gao, Ge & Wu, Xia & Wang, Xiao-Min & Yang, Hui. (2015). Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury. Brain research. 1639. 10. 1016/ j. brainres. 2015. 07. 029. Currently, available treatment approaches for Parkinson’s disease (PD) are limited in terms of variety and efficacy. Piper longum L. (PLL; Piperaceae) is used in traditional medicine in Asia and the Pacific Islands, with demonstrated anti-inflammatory and antioxidant activities in preclinical studies, and alkaloid extracts of PLL have shown protective effects in PD models. The present study investigated the mechanistic basis for the observed protective effects of PLL. Rats treated with PLL-derived alkaloids showed improvement in rotenone-induced motor deficits, while reactive oxygen species (ROS) production was decreased, mitochondrial membrane potential was stabilized, and the opening of the mitochondrial permeability transition pore (mPTP)-which is involved in ROS production inhibited. In addition, rotenone-induced apoptosis was abrogated in the presence of these alkaloids, while pretreatment stimulated autophagy, likely mitigating neuronal injury by the removal of damaged mitochondria. These findings provide novel insight into the neuroprotective function of PLL as well as evidence in favor of its use in PD treatment.
• He, Huan & Guo, Wei-Wei & Xu, Rong-Rong & Chen, Xiao-Qing & Zhang, Nan & Wu, Xia & Wang, Xiao- Min. (2016). Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide. BMC Complementary and Alternative Medicine. 16. 10. 1186/ s12906- 016- 1392-6. Alkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by inhibiting microglial activation using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model. The animal behaviors of rotational behavior, rotarod test, and open-field test were investigated. The survival ratio of dopaminergic neurons and microglial activation were examined. The dopamine (DA) and its metabolite were detected by high-performance liquid chromatography (HPLC). The effects of PLA on the expression of interleukin (IL)- 6, interleukin (IL)- 1β, and tumor necrosis factor (TNF)- α were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and nitric oxide (NO) were also estimated. Results- We showed that the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were reduced after a single intranigral dose of LPS (10 μg) treatment. The survival rate of TH-ir neurons in the SNpc and DA levels in the striatum were significantly improved after treatment with PLA for 6 weeks. The over-activated microglial cells were suppressed by PLA treatment. We also observed that the levels of inflammatory cytokines, including TNF-α, IL-  6, and IL-1β were decreased and the excessive production of ROS and NO were abolished after PLA treatment. Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment. Conclusion- This study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction-induced damage.
• Inchan, Anjaree & Promma, P & Yoysungnoen, Bhornprom & Chootip, Krongkarn. (2008). Cardiovascular action of Piper longum. Planta Medica – PLANTA MED. 74. 10. 1055/ s- 0028- 1084014. Cardiovascular actions of various plants from the Piperaceae family were reported, but little is known about the action of long pepper (Piper longum). Therefore, we aimed to investigate the effects of long pepper ethanolic extract on rat blood pressure (BP) i.e. systolic (Ps), diastolic (Pd), mean arterial pressure (MAP), heart rate (HR), and isolated aorta. Intravenous administration of the extract (1, 5, 10mg/Kg BW) significantly decreased Ps, Pd, MAP, and HR in anesthetized rats. Administration of extract (1mg/kg BW) produced the most pronounced hypotensive effect. The higher the doses of the extract used, the lower the % decreases in blood pressure were observed. At all dose studies, % decreases in Pd were significantly greater than that in Ps (P< 0.05). HR was significantly decreased at all doses, but the changes appeared to be dose independent. The extract (0.005– 0.5 mg/ ml) induced relaxation in endothelium intact and denuded aorta pre-contracted with either 1µM PE or 80 mM K+. Relaxation of endothelium intact artery was more pronounced than that of the endothelium-denuded artery (P< 0.05). Pretreatment of aorta with 100 µM NG- nitro- L- arginine methyl ester or 10µM indomethacin significantly reduced relaxation induced by the extract (P< 0.05). In the Ca++-free medium, pre-incubation of the aorta with the extract (0.5 mg/ ml) significantly decreased the contractile response induced by CaCl2 (1 to 5x mM). In conclusion, the results indicated that long pepper possessed hypotensive and vasodilator action in rats. The mechanism of vasodilation involved both nitric oxide and prostacyclin pathways as well as inhibition of extracellular calcium entrance into arterial smooth muscle cells. This research was funded by the National Research Council of Thailand. References: 1. Martin, H.B. et. al. (2002) Planta. Med. 68:784–789. 2. Raimundo, J.M. et. al. (2004) J. Pharm. Pharmacol. 56:1457–1462. 3. Runnie, I. et. al. (2004) J. Ethnopharmacol. 92: 311– 316.
• Wakade, AS & Juvekar, Archana & Kulkarni, Mp & Shah, AS. (2007). Protective effect of Piper longum fruits against experimental myocardial oxidative stress-induced injury in rats. Planta Medica – PLANTA MED. 73. 10. 1055/ s- 2007- 987222. The present study investigated the protective effect of methanolic extract of fruits of Piper longum L. (PLM) on isoproterenol (ISO) induced myocardial infarction in rats. PLM was administered to Wistar albino rats in two different doses, by gastric gavage for 28 days. Myocardial infarction was induced by subcutaneous administration of ISO for 2 days at the end of the dosing period. ISO administration resulted in a significant decrease in the activities of marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) in the heart with a concomitant increase in their activities in serum. A significant increase in lipid peroxide levels (TBARS) in the hearts of ISO-induced rats was also observed. Activities of myocardial antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOX), and glutathione reductase (GR) along with reduced glutathione (GSH) were significantly lowered owing to myocardial infarction in ISO treated rats. PLM pretreatment was found to ameliorate the effect of ISO on lipid peroxide formation and retained activities of marker enzymes. It also prevented an ISO-induced decrease in antioxidant enzymes in the heart. Histopathological studies of the heart revealed a protective role of PLM in ISO-treated rats. The results exhibited that the pretreatment with methanolic extract of Piper longum fruits may be useful in preventing the damage induced by ISO in rat hearts.
• Mamun, Al & Khatun, Hajera & Islam Ph.D., Md Rafikul & Nahar, Laizuman & Shams Ud Doha, Km & Ripa, Farhana. (2014). EVALUATION OF CNS DEPRESSANT AND ANALGESIC ACTIVITIES OF THE METHANOL EXTRACT OF PIPER LONGUM LINN. LEAVES. International Journal of Pharmaceutical Sciences and Research. 2. 2874-2879. The present study reports CNS depressant and analgesic activities of methanol extract obtained from the leaves of Piper longum L (MEPL). CNS depressant activity was evaluated by using open field and hole cross tests at doses of 250 and 500 mg/kg body weight while peripheral analgesic activity was evaluated by using acetic acid induced writhing method and formalin test respectively in rat model at 100 and 200 mg/ kg body weight. The results of the statistical analysis showed that the plant extract had significant (p< 0.01) dose-dependent CNS depressant and analgesic activities. Locomotor activity and exploratory behavior of rats in hole cross and open field tests were decreased in the test group comparing the control group indicating the CNS depressant effect of the extract which was comparable with the standard drug diazepam. The extract also showed better analgesic effects at both doses characterized by a reduction in the number of writhes in the acetic acid-induced writhing model and a reduction of licking time in the formalin test when compared to the control group. The extract, at the dose of 200 mg/ kg, exerted a maximum of 57.58 % inhibition of writhing response and 58.8 % inhibition was observed for reference drug Indomethacin. So, the present results suggest that the methanol extract of P. longum leaves possesses remarkable CNS depressant and analgesic activities. 
• C, Surya & Shanmugam, Rajeshkumar & Thangavelu, Lakshmi & Roy, Anitha. (2022). Antidiabetic Activity of Piper Longum and Stevia Herbal Formulation. Journal of Complementary Medicine Research. 13. 29. 10. 5455/ jcmr. 2022. 13. 03. 06. AIM: The aim of the study is to find the antidiabetic activity of piper longum and stevia herbal formulation. Diabetes Mellitus, also known as diabetes is a metabolic disorder that is characterized by increased blood glucose levels. Frequent urination, increased thirst, and increased appetite are the common symptoms. Three types of diabetes, namely type 1, type 2, and gestational diabetes. Piper longum, also known as Indian long pepper, belongs to the family Piperaceae. It belongs to the Indo-Malaya region and tropical rainforest region. Stevia rebaudiana commonly known as candy leaf, sweet leaf, and sugar leaf belongs to the genus Stevia. Stevia is a natural sweetener and natural sugar substitute. MATERIALS AND METHOD: alpha-amylase inhibition was determined by quantifying the amount of maltose liberated during the experiment. Different concentrations of nanoparticles (10, 20, 30, 40, 50 L.) were pre-incubated with 100 L of amylase solution (1U/mL) at room temperature for 30 minutes. DNSA reagent was added to stop the reaction, and the solution was heated in a water bath for 5 minutes. Control was maintained where the equal quantity of enzyme extract was replaced by sodium phosphate buffer maintained at a pH value of 6.9. RESULTS AND DISCUSSION: The bar graph represents the antidiabetic activity of piper longum and stevia herbal formulation in various concentrations in L. 10 % L concentration shows 45 % inhibition, 20 % L of concentration shows 50 % inhibition, 30 % of concentration shows 65 % of inhibition, 40 % of concentration shows 70 % of inhibition and 50 % of concentration shows 80 % of inhibition. CONCLUSION: From this study, the fruit of piper longum and stevia leaves has proven to be a better choice for antidiabetic activity.
• Kumar, Suresh & Sharma, Sunil & Vasudeva, Neeru. (2013). Screening of antidiabetic and antihyperlipidemic potential of oil from Piper longum and piperine with their possible mechanism. Expert opinion on pharmacotherapy. 14. 10. 1517/ 14656566. 2013. 815725. Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and other symptoms like polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger) which ultimately causes various other complications like retinopathy, neuropathy, nephropathy, and microangiopathy. Objectives: The antidiabetic and antihyperlipidemic potential of oil from Piper longum (PLO) and piperine was investigated with their possible mechanism using α-glucosidase, aldose reductase (AR), and pancreatic lipase inhibitory activity. Methods:  The biochemical parameters, viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride, and antioxidant parameters, were estimated for all treated groups in acute and chronic antihyperglycemic animal models. Results: PLO (100 and 200 mg/ kg), piperine (25 and 50 mg/ kg), and glibenclamide (0.6 mg/ kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-induced diabetic rats. There was a significant increase in body weight, liver glycogen content, plasma insulin, and high-density lipoprotein and a decrease in glycosylated hemoglobin, triglyceride, and total plasma cholesterol in PLO- administered groups as compared to the control group. The IC50 value of PLO for α-glucosidase, AR, and pancreatic lipase was found to be 150 ± 2.5, 120 ± 1.2, and 175 ± 1.2 μg/ ml, respectively, which was found comparable with the standard drugs acarbose (90 ± 2.3 μg/ ml), quercetin (80 ± 2.3 μg/ ml), and orlistat (25 ± 0.5 μg/ ml), respectively. Conclusion: The investigation reveals that PLO has significant antidiabetic and antihyperlipidemic activity.
• Prasad, Mrinalini & Singh, Anjali & Yadav, Arti & Singh, Teg & Goyal, Deepika & Shrivastav, Preksha & Dantu, Prem & Prem, Correspondence & Dantu, Kumar. (2018). Analysis for piperine in leaves, roots, and spikes in Piper longum L. Piper longum L (Pipali) is an important medicinal plant used as an analgesic, antipyretic, CNS depressant, anti-inflammatory, anti-tumor, sedative, hypnotic, tranquilizer and muscle relaxant, hepatoprotective both in digestive and respiratory systems. The fruit of Piper longum contains a large number of alkaloids and related compounds, among them the most important is piperine. Attempts were made to detect piperine in different parts of the Piper longum plant. Leaf and roots of both male and female plants and spikes from only female plants were used. Methanol extracts of the above-mentioned parts were prepared and subjected to thin-layer chromatography (TLC) along with piperine as a standard, using toluene- ethyl acetate (70: 30) mobile phase. Upon treatment with vanillin-sulphuric acid reagent and subsequent heating the silica gels and viewed under UV light. The appearance of yellow fluorescence was observed in all the samples except the male leaf. This confirmed the presence of piperine in all parts except the male leaf of the Piper longum plant.
• Chauhan, Khushboo & Parmar, Lipsa & Solanki, Richa & Kagathara, V. & Madat, D. & Patel, T. (2010). Effect of Piper longum Linn on histopathological and biochemical changes in isoproterenol-induced myocardial infarction in rats. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 1. 759- 766. In this study, the cardioprotective effect of methanolic extract of Piper longum (MePl) was evaluated in a rat model having acute myocardial infarction, induced by Isoproterenol (ISO) (85 mg/ kg, sc, for two consecutive days). MePl (250 mg/ kg and 500 mg/ kg) pretreatment orally for 28 days significantly prevents the damage induced by isoproterenol and is supported in histopathological examination evinced by decreased vascular and fatty degeneration, granular disintegration and hyaline necrosis of muscle fibers. The results of histopathological examination of the rat’s heart sections confirmed the myocardial injury which was further supplemented by biochemical observations like decreased levels of Creatine Kinase-MB (CKMB) and Lactate dehydrogenase (LDH) as serum myocardial markers. The results were comparable to that of the ascorbic acid-treated group. The present results provide evidence for the first time that MePl pretreatment prevents myocardial injury against ISO-induced myocardial infarction in rats.