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Piper longum L. Scientific Name: Piper longum L. Synonyms: Chavica longa H. Karst, Chavica roxburghii Miq, Chavica sarmentosa Miq. Family: Piperaceae Genus: Piper Species: P. longum Common Name: Indian Long Pepper, Indonesian Long Pepper, Dried Catkins, Pippali, Pipal, Tippli, Pihal, Javanese Long Pepper. Plant Description: P. longum is a slender aromatic climber, with a large perennial woody root and jointed stems thickening at the nodes. The dark, dentate leaves are ovate and heart-shaped, about 2 to 3 inches in length, with broad rounded lobes at the base. The flowers are monoceous and male and female flowers are borne on different plants. The fruits are ovoid, yellowish-orange, minute, and drupe around 1 inch in diameter. The spikes are red when ripe and turn to black on drying. Spikes are pedunculate and upright; male larger and slender; female 1.3-2.5 cm long and 4-5 mm in diam. Used: Dried unripe fruits, root, stem Chemical Constituents: Volatile oil, resin, piperine, piperlongumine, piplasterol, pippalartin, piplartine, sylvatin, sesamin, diaeudesmin, piperlingumine, pipermonaline, piperundecalidine, brachyamide A, brachyamide B, brachystine, sterols, glycosides. Essential oil.Mono and sesquiterpenes, caryophyllene (mainly), Pipernonaline, Pipercide, Sesamin, B- sitosterol four aristolactams(cepharanone B. aristolactum A- ll. Piperlactum A and piperolactam B) five 4-5 dioxoaporphines etc.

Chemical constituents isolated from Piper longum L.

Piperine Piperlongumine

Brachyamide B Caryophyllene

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Pipernonaline Asarinine Actions of Herb: Analgesic, anti-pyretic, anti-inflammatory, anti-hyperglycemic, anti-lipidperoxidative, anti-oxidant, anti-diabetic, anti-hypertensive, anti-platelet, anti-tumor, anti-asthmatics, anti-diarrheal, anti-spasmodic, anti-depressants, immunomodulatory, anti-convulsant, anti-thyroids, anti-bacterial, anti-fungal, hepato-protective, insecticidal, larvicidal activities, abortifacient, alterative, anti-epileptic, anti-flatulent, aphrodisiac, astringent, calorific, carminative, detersive, diuretic, emmenagogue, errhine, expectorant, resolvent, rubefacient, stimulant, stomach tonic and vermifuge. Medicinal Uses: P. longum helps in expelling out the mucus accumulated in the respiratory tract. It strengthens the nervous system, improves the gastrointestinal condition and normalizes the peristaltic movements. The herb serves as a good digestive agent. Its oil and paste is applied on wounds and skin-related ailments. P. longum helps in suppressing pain and reducing inflammation. The herb helps maintain the normalcy of the digestive tract and tones up the urinary tract. Its fruits are used for respiratory tract diseases like cough, bronchitis and asthma. It benefits in anorexia, indigestion, flatulence, abdominal pain, hyperacidity, piles, paralysis of the tongue, diarrhea, cholera, chronic malaria, viral hepatitis, diseases of the spleen and tumors. It is given to treat anemia. The decoction of the plant is used in sciatica and hemiplegia. The herb is mixed with honey to control hiccups. P. longum is used as an aphrodisiac, since it boosts the reproductive system. It is used as a sedative in insomnia and epilepsy. The infusion of the herb’s root is used after childbirth, to induce the expulsion of the placenta. Dosage: Powder- 500 mg to 1 gmin a single or multiple doses per day usually administered after food. Side effects: Skin rashes, intestinal inflammation and small increases in liver enzymes.

Contraindications: Pregnancy and lactation. Drug Interactions: Phenytoin (Dilantin) interacts with P. nigrum: Indian long pepper might increase how much phenytoin (Dilantin) the body absorbs. Taking Indian long pepper along with phenytoin (Dilantin) might increase the effects and side effects of phenytoin (Dilantin). Propranolol (Inderal) interacts with P. nigrum: Indian long pepper might increase how much propranolol (Inderal) the body absorbs. Taking Indian long pepper along with propranolol (Inderal) might increase the effects and side effects of propranolol (Inderal). Theophylline interacts with P. nigrum: Indian long pepper can increase how much theophylline the body absorbs. Taking theophylline along with Indian long pepper might increase the effects and side effects of theophylline. Phytochemical analysis of P. longum Trivedi et al. (2011) carried out phytochemical analysis of P. longum.

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Table: Phytochemical analysis of P. longum

Trivedi MN, Khemani A, Vachhani UD, Shah CP,Santani DD. 2011.Pharmacognostic, phytochemical analysis and

antimicrobial activity of two Piper species. Pharmacie Globale, (IJCP); 7 (5): 1-4. Microscopic evaluation of P. longum Vinay et al. (2012) carried out microscopic examination of spike of P. longum.

Table: Diagnostic microscopic characters of P. longum spikes

Vinay S, Renuka K, Palak V, Harisha CR, PrajapatiPK. 2012. Pharmacognostical and Phytochemical study of Piper

longum L. and Piper retrofractum Vahl. Journal of Pharmaceutical and Scientific Innovation; 1(1): 62-66.

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Parenchyma with oil globules Stone cells

Fibers Starch grains, prismatic crystals & epidermal cells

Figures: Diagnostic microscopic characters of P. longum Chaudhari VM, Manjusha R, Dhiman KS, Harish CR, Shukia VJ. 2011. A preliminary pharmacognostical and

physic-chemical assay of PippalyadiTaila – A pilot study. International Journal of Science Innovations and Discoveries; 1(3): 386-394.

Physio-chemical evaluation of P. longum Vinay et al. (2012) carried outphysic-chemical analysis of P. longum fresh and old fruits. See the table below.

Table: Physio-chemical evaluation of P. longum

Vinay S, Renuka K, Palak V, Harisha CR, PrajapatiPK. 2012. Pharmacognostical and Phytochemical study of Piper

longum L. and Piper retrofractum Vahl. Journal of Pharmaceutical and Scientific Innovation; 1(1): 62-66. Water and alcohol soluble extractive value of root and stem extracts of P. longum were evaluated by Nitin et al. (2012). See the table below.

Table: Percentage of water soluble and alcohol soluble extractives

Nitin UBL. Vivek P, Remadevi R. 2012. A comparative phytochemical screening of root and stem of Piper longum

L. International Journal of Researc in Ayurveda and Pharmacy; 3(1): 67-69.

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Thin-layer chromatography of P. longum Nitin et al. (2012) carried out thin-layer chromatography of methanolic extracts of root and stem of P. longum and spots were visualized under UV lamp at 254nm and 366nm respectively.

Table: Thin-layer chromatography of methanolic extracts of stem and root of P. longum at 366nm.

Nitin UBL. Vivek P, Remadevi R. 2012. A comparative phytochemical screening of root and stem of Piper longum

Linn. International Journal of Research in Ayurveda and Pharmacy; 3(1): 67-69.

Figure: Thin-layer chromatography of methanolic extracts of stem and root of P. longum.

Nitin UBL. Vivek P, Remadevi R. 2012. A comparative phytochemical screening of root and stem of Piper longum L. International Journal of Research in Ayurveda and Pharmacy; 3(1): 67-69.

High Performance Thin-layer Chromatography of P. longum Vinay et al. (2012) carried out physic-chemical analysis of P. longum fresh and old fruits.

Table: High Performance Thin-layer chromatography of P. longum

Vinay S, Renuka K, Palak V, Harisha CR, Prajapati PK. 2012. Pharmacognostical and Phytochemical study of Piper

longum L. and Piper retrofractumVahl. Journal of Pharmaceutical and Scientific Innovation; 1(1): 62-66.

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Fourier transform infra-red spectroscopy of P. longum Mishra (2010) carried out FT-IR spectroscopy of P. longum.

Figure: FT-IR spectra of P. longum

Mishra P. 2010.Isolation, spectroscopic characterization and computational modeling of chemical constituents of Piper longum natural product. International Journal of Pharmaceutical Sciences Review and Research;2(2): 78-86.

1H-NMR spectroscopy of P. longum Mishra (2010) carried out 1H-NMR spectroscopy of P. longum.

Figure: 1H-NMR spectra of isolated compounds from P. longum

Mishra P. 2010.Isolation, spectroscopic characterization and computational modeling of chemical constituents of Piper longum natural product. International Journal of Pharmaceutical Sciences Review and Research;2(2): 78-86.

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Mass spectroscopy of P. longum Mishra (2010) carried out mass spectroscopy of P. longum.

Figure: TOF-Mass spectra of isolated compound of P. longum.

Mishra P. 2010.Isolation, spectroscopic characterization and computational modeling of chemical constituents of Piper longum natural product. International Journal of Pharmaceutical Sciences Review and Research; 2(2): 78-86.

Anti-microbial activity of P. longum Vinay et al. (2012) carried out anti-microbial activity of aqueous and methanolic extracts of P. longum.

Table: Anti-microbial activity of P. longum

Trivedi MN, Khemani A, Vachhani UD, Shah CP, Santani DD. 2011.Pharmacognostic, phytochemical analysis and

antimicrobial activity of two Piper species. Pharmacie Globale (IJCP); 7 (5): 1-4.

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Anti-oxidant activity of P. longum Anu et al. (2013) carried out anti-oxidant activity of different fractions of fruit extract of P. longum by using In vitro anti-oxidant assay models like phosphomolybdenum and reducing power assay. See the figures below.

Figure: Reducing power assay of different fruit extracts of P. longum

Figure: Pospho-Molybdenum assay of different fruit extracts of P. longum

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Analgesic activity of P. longum Ashajyothi and Jabeen (2014) evaluatedthe analgesic effect of ethanolic extract of P.longum fruits in experimental models of pain via narcotic model tail immersion tests (central analgesic method).The results of the study revealed that the P. longumv extract possess significant analgesic activity as perceived by increase tail withdrawal latencies in tail immersion test as compared to the control group. Table: Analgesic activity of ethanolic extract of Piper longum fruits in Sprague dawley rats.

All values are expressed as mean ± SEM (n = 6); one-way analysis of variance (ANOVA) followed by Dunnet’s multiple comparison test. P < 0.01 significance compared to control.

Ashajyothi V, Jabeen S. 2014. Phytochemical evaluation and pharmacological screening for analgesic activity of ethanolic extract of Piper longum. Research Journal of Pharmacy; 2(1): 1-6.

In vitro and In vivo anti-asthmatic studies on P. longum Petroleum ether extract of P. longum fruit(PF), alcoholic extract of P. longum fruit (AF), decoction of P. longum fruit (DF) were evaluated for their anti-asthmatic activity by Kaushik et al. (2012) using in vitro and in vivo models such as isolated Guinea pig ileum preparation (in vitro), histamine-induced bronchospasm in Guinea pigs, milk-induced leukocytosis in mice, haloperidol-induced catalepsy in mice and passive paw anaphylaxis in rats (in vivo).The tested extracts were found to be effective in all models of asthma, hence exhibited significant anti-asthmatic activity. Anti-diabetic and anti-hyperlipidemic activity of P. longum Nabi et al. (2013) evaluated anti-diabetic and anti-hyperlipidemic activity of P. longum aqueous root extracts in streptozotocin (STZ) induced diabetic rats. During the short term study the aqueous extract at a dosage of 200 mg/kg was found to possess significant anti-diabetic activity after 6 hours 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 fasting blood glucose 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 property and hence safe and effective use of P. longum in the treatment of diabetes. Hepato-protective effect of P. longum Patel and Shah (2009) investigated the hepato-protective activity of P. longum milk extract. Carbon tetrachloride was used as a hepatotoxin at a dose of 0.5 ml/kg p.o. with olive oil (1:1) thrice a week for 21 days to produce the chronic reversible type of liver necrosis. Following treatment with P. longum milk extract (200 mg/day p.o. for 21 days), a significant hepato-protective effect was observed in CCl4 induced hepatic damage as evident from decreased level of serum enzymes, total bilirubin and direct bilirubin. The hepato-protective effect of P. longum is comparable to the standard drug, Silymarin (25 mg/kg/day p.o. for 21 days).

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Patel JA, Shah US. 2009. Hepatoprotective activity of Piper longum traditional milk extract on carbon tetrachloride induced liver toxicity in Wistar rats. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 8 (2), 121 – 129. Anti-fertility activity of P. longum Garg et al. (1981) administered P.longum roots and E. ribes seeds on days 4 to 7 and 6 to 9 of pregnancy revealing 100% anti-fertility activity in female albino rat. Anti-amoebic effect of P. longum Sawangjaroen et al. (2004) evaluated the anti-amoebic effects of crude methanol extract of P. longum fruit against Entamoeba histolytica infecting the caecum of mice. The results of the study exhibited dose-dependent anti-amoebic effects.

Table: Effect of crude methanol extract of P. longum fruit on caecal amoebiasis in mice

a = Caecal scores were graded upon the following criteria, Neal (1951). Wall: normal, 0; slight thickening, 1; marked local thickening and contraction, 2; extensive thickening and contraction, 3; caecum shapeless (extensive ulceration with abscess formation), 4. Contents: normal, 0; slightly less solid than normal, 1; slightly mucoid, 2; mucoid (some solid matter present), 3; no solid matter (white or yellow mucus only), 4. Sawangjaroen N, Sawangjaroen K, Poonpanang P. 2004. Effects of Piper longum fruit, Piper sarmentosum root and

Quercus infectoria nut gall on caecalamoebiasis in mice. Journal of Ethnopharmacology; 91: 357–360. Anti-cancer activity of P. longum The anticancer activity of the different extracts of fruits of P.longum on human lung epithelial adenocarcinoma cell line (HCC-827) has been assessed in vitro using 3‐(4,3,5‐dimethylthiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide (MTT assay). The potency of plant extracts to inhibit the cancerous growth was recorded in terms of decrease in viable cell count as compared to the control value. The inhibition of the growth of human lung epithelial adenocarcinoma cell line (HCC-827) has been found to be dose dependent. Phalloidin staining of the control and treated cells were performed to check the changes in the structure of cytoskeleton which appeared to be distorted and disorganized in control as compared to treated cancerous cells. Insecticidal activity of P. longum Lee (2000) carried out insecticidal activity of methanolic extract of P. longum fruit. The results of the study revealed that a methanol extract of P. longum fruit was found to be active against mosquito larvae of Culexpipien spallens at l0 µg/ml after 24 h. Anti-rheumatoid activity of P. longum Yende et al. (2010) carried out anti-rheumatoid activity of the fruits of P. longum in Freunds adjuvant induced arthritis rats at the dose of 200 and 400 mg/kg p. o, respectively. The administration of P. longum extract showed significant reduction in paw swelling on 4th, 8th, 14th and 21st day after sub-planter administration of Complete Freunds adjuvant. The paw swelling was measured as a volume displacement using digital Plethysmometer. Furthermore, these results supported by radiographic analysis of affected knees of rats. The results of the research work exhibited that the aqueous extract of P. longum possesses significant anti-arthritic activity in Complete Freunds Adjuvant model.

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Cognitive enhancing activity of P. longum Madhaviet al. (2012) investigated the cognitive enhancing activity of ethanolic fruit extract of P. longum by using two methods; elevated plus maze and passive avoidance task methods. The results of the study showed significant effect as compared to control; there was significant increase in the step down latency and decrease in the transfer latency, revealing cognitive enhancing activity of P. longum.

Table: Mean Values of Transfer latency of various drug treated groups

Madhavi DB, Kumar KLS, Palanivel V. 2012. Evaluation of Cognitive Enhancing Activity of Piper longum Fruit

Extract on Albino Rats. International Journal of Pharmaceutical and Chemical Sciences; 1 (3): 1057-1061. Table: Mean Values of step down latency of various drug treated groups

Madhavi DB, Kumar KLS, Palanivel V. 2012. Evaluation of Cognitive Enhancing Activity of Piper Longum Fruit

Extract on Albino Rats. International Journal of Pharmaceutical and Chemical Sciences; 1 (3): 1057-1061. Chronotropic and Inotropic effects of P. longum: Lokhande et al. (2006) isolated four fractions namely F, G, H and I from root of P. longum Linn. and studied their effects on isolated frog heart. Fraction F produces negative chronotropic effect on isolated frog heart. Fraction F blocks the actions of adrenaline completely at 200 µgmL-1.The heart rate and force of contraction decreased in a dose dependent manner. Fraction F acts as antagonist of beta adreno-receptors. It blocks the actions of adrenaline in a dose dependent manner. The hexane extract of root of P. longum was comparatively found to be less active than fraction F. the present study revealed the β-antagonistic activity of the isolated fractions from P. longum. References Ashajyothi V, Jabeen S. 2014. Phytochemical evaluation and pharmacological screening for analgesic activity of

ethanolic extract of Piper longum. Research Journal of Pharmacy; 2(1): 1-6. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. 2002. Piperine, a major constituent of

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Chaudhari VM, Manjusha R, Dhiman KS, Harish CR, Shukia VJ. 2011. A preliminary pharmacognostical and physico chemical assay of PippalyadiTaila – A pilot study. International Journal of Science Innovations and Discoveries; 1(3): 386-394.

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Patel JA, Shah US. 2009. Hepatoprotective activity of Piper longum traditional milk extract on carbon tetrachloride induced liver toxicity in Wistar rats. Boletín Latino-americano y del Caribe de Plantas Medicinales y Aromáticas, 8 (2), 121 – 129.

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Sawangjaroen N, Sawangjaroen K, Poonpanang P. 2004. Effects of Piper longum fruit, Piper sarmentosum root and Quercusinfectoria nut gall on caecalamoebiasis in mice. Journal of Ethnopharmacology; 91: 357–360.

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Yende SR, Sannapuri VD, Vyawahare NS, Harle UN. 2010. Anti-rheumatoid activity of aqueous extract of Piper longum on Freunds adjuvant-induced arthritis in rats.Int J Pharm Sci& Res; 1(9): 129-133.