International Journal of Scientific Research and Review ISSN NO: 2279-543X

A Traditional miraculous drug longum : Review Hana Abbasi*, Hifzul kabir P.G.Scholar, Assistant Professor, Deptt. Of Ilmul Advia, School of Unani Medical Education and research, Jamia Hamdard, New Delhi, 110062.

ABSTRACT Piper longum, common name , pippali belonging to family is a slender aromatic climber with perennial woody roots found in hotter parts of . Long pepper has been used by tribals for improved cardiovascular functions and as a spice. parts such as fruits, leaves, roots and stem show a variety of pharmacological actions like analgesic, immunomodulatory, hepatoprotective activity, anti inflammatory and anti fertility. It has been utilized vividly in treatment of bronchitis, liver fibrosis, allergies and digestive diseases. Major chemical constituents are alkaloids, lignans and volatile oils.

KEYWORDS: Piper longum, analgesic, anti inflammatory, pippali.

INTRODUCTION In the present world conditions, there is a widespread of diseases which can easily tear down the day to day life of human being. Nowadays most of the population due to lifestyle diseases depends upon a number of drugs to lead a healthy life. In allopathic medicine, there is a mass production of chemically synthesized drugs which has revolutionized the health care sector but at the same time it also influences the physical and economic status of people, according to World Health Organization (WHO) about 70 to 80 percent of world population depend upon herbal medicines. Use of herbs is very much common because it is affordable, cheaper, diminishes concerns about the adverse effects of chemical medicines, fulfills the desire for more personalized health care, allows better public access to health information and easy availability. 1 There are a large variety of herbal medicines which can be used for prevention and cure of different diseases. In the present article we have discussed about the benefits of Piper longum. Piper longum is the plant in which all the parts of the plant are used as remedy.There are many uses of Piper longum mentioned in classical literature of traditional medicine whether it is Unani system or Ayurvedic system of Medicine. Different terms are used in different systems such as “filfil daraaz” in Unani and “Pippali” in Ayurveda.Several scientific studies have been conducted with Piper longum to prove its therapeutic actions. The whole plant has been reported to acquire hypoglycemic, antispasmodic, cough suppressant and medullary stimulant effects. 2, 3, 4, 5, 6 The fruit exihibit antiallergic effect, hepatoprotective, intestinal tonic, antiamoebic activity, anti inflammatory activity and anti depressant activity. 2,7,8 Roots are mainly used as analgesic and anti fertility drug.2,9 Piper longum is commonly used as a spice which increases the taste of the food, turn out salivation and numbness of the mouth but at the same time it also serves as a remedy with several medicinal benefits. 10

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Taxonomical Classification Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Family: Piperaceae Genus: Piper Species: longum Botanical name: Piper longum11 Vernacular names Arabic: Darfilfil, Bengali: Piplamor, piplamul, pipli, pipul, Burma: peikchin, Chinese: pi po, Deccan: pipplie, Dutch: Langwerpige peper, English: long pepper, French: Poivre long, German: langer pfefer, Greek: peperi makron, Gujuarati: Pipli Hindi: papal, Pipar, piplamul Hungarian: Bengáli bors Italian: Pepe lungo Kannada: Hippali, Lippali, Thippili, Malayalam: Magadhi, Pippali, Thippili, Tippili, Marathi: Pimpli Nepal: popal, Gaj pipla, Saano pipla, Portuguese: Pimenta-longa, Swedish: Långpeppar, Tamil: argadi, Kandan lippilli, pippili, sirumulam, tippili, thippili, Telugu : Pippallu, Urdu: Pipul. 11, 12

Distribution The incident of Piper longum mainly found in hotter areas of India, from central Himalayas to Assam. There are two or three species of Piper longum sold in India out of which one variety came from . Wild of Piper are the main source of supply which comes from West Bengal, Nepal, and Uttar Pradesh. It’s also cultivated in low elevations in Anaimalai hills in Madras and in limestone soil of Cherrapunji. 11, 13 DIFFERENT PARTS OF PIPER LONGUM PLANT

IMMATURE BERRIES DRIED FRUIT

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FRESH FRUIT PLANT Description Piper longum is a small shrub with diocious slender aromatic climber having perennial woody roots clasping at nodes which helps it to get attached to host trees. 7,8,11,14

Roots: The rootstock is erect, thick, jointed and branched. The roots are adventitious, upto 9 cm long; surface dark brown with few rootlet scars. In T.S. the root shows thin walled and rectangular to slightly creatively elongated cork cells. Most of the cortical cells contain spherical or oval starch grains. A few cortical cells contain minute prismatic crystals of calcium oxalate. 7,8,11,14

Stem: Numerous, 0.6 to 0.9m in length, ascending or prostrate highly branched, stout, cylindrical, thick at above nodes and finely pubescent. 7,8,11,14

Leaves: 6.3 to 9cm in length, numerous, lower one is broadly ovate, cordate at base, all sub acute entire leaves, glabrous, thin with reticulate venetion. Leaves are sunk above and raised beneath, dark green shining adaxial surface, pale and dull abaxial surface, petiole of lower leaves 5 to 7.5cm long, stout with very short upper leaves or none, stipule about 1.3cm, membranous, lanceolate, obtuse and soon fallen. 7,8,11,14

Fruits: It contains a small blackish green ovoid fruit which completely sunk in solid fleshy spike. Fruit is about 2.5 to 3.8cm with a shining surface.It is erect, oblong, and blunt with an aromatic odour and pungent taste.7,8,11,14 Parts Used Immature berries, stems roots. 12 Temperament Hot2 and Dry2. 12 Taste Bitter and strong.20 Actions Mufatteh sudad (deobstruent) 15,16,17,18 Hazim ghiza (digestive) 15,16,17,18 Muqavvi meda (gastric tonic) 15,16,17,18 Dafe qai (anti vomitic) 15,16,17,18

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Muqavvi bah (aphrodisiac) 15,16,17,18 Mughalliz mani (semen viscositive) 15,16,17,18 Mudir bol (diuretic) 15,16,17,18 Mudir haiz (emmenagogue) 15,16,17,18 Musakkit janeen (abortifacient) 15,16,17,18 Musakhkhin ahshah (calorific of membrane) 15,16,17,18 Kasir riyah (carminative) 15,16,17,18 Mohallile nafakh (flatulence resolvent) 15,16,17,18 Mulattif (demulcent) 15,16,17,18 Munaffis (expectorant) 15,16,17,18 Muteebe reham (bad odour of uterus) 15,16,17,18 Musakhkhin reham (calorific of uterus) 15,16,17,18 Musaffi dam (blood purifier) 15,16,17,18 Dafe tashannuj (antispasmodic) 15,16,17,18 Mushtahi (appetizer) 15,16,17,18 Mohallile auram (resolvent) 15,16,17,18 Muallid safra (bile procreator) 15,16,17,18 Muhammir (rubefaecient) 15,16,17,18

Main action

Amraz barid ratab (coldwet diseases) 17, 18, 20

Amraz e jigar wa meda (liver and stomach diseases) 17, 18, 20

Uses

Falij (paralysis)

Laqwa (Palsy)

Sara (epilepsy)

Bronchitis

Nuqras (gout)

Irq un nisa (sciatica)

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Dama (asthama)

Auram (inflammations)

Hichki (hiccough)

Jigar wa tihaal k sudde (Obstruction of liver and spleen)

Zauf e ishteha (loss of appetite)

Zauf e meda (gastric weakness)

Muteeb e dahan (halitosis)

Zauf e bah (anaphrodisia)

Rataundi (night blindness)

Nafakh e shikam (flatulence),

Spleenomegaly

Pain in joints

Balgami khansi (chronic cough).11, 12, 15, 17, 19

Dose 4.36 gm 16 1.75 to 4.5 gm 17 4 gm 20 5.82 gm 18 0.97 to 1.94 gm 19 Toxicity Head (causing headache), bladder, lungs.15, 17, 18, 19 Correctives Samag e arbi (gum of acacia) Sandal (Santalum album) Gulab (Rosa rubiginosa Isapgol (Plantago ovate) Shahad (honey).15, 17, 18, 19, 20

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Substitute zanjabeel (Zingiber officinale) zarnabad (Zingiber zerumbet Rosc. Ex Smith.). 15, 17, 18, 19, 20

Compound formulations Jawarish Jalinoos Jawarish Bisbasa Jawarish kamooni Majoon Filasfa. 20, 21

PHYTOCHEMISTRY The chief constituents of Piper longum are alkaloids, volatile oil, resin, starch, gum, fatty oils and inorganic matter.12 There is a large number of alkaloids present in it, the most copious of which is piperine, followed by methyl piperine, piper- nonaline, piperettine, asarinine, pellitorine, pipe- rundecalidine, piperlongumine, piperlonguminine.9 Essential oil from the fruits of P. longum is β- caryophyllene (10.2%).22 The inflorescences oil is rich in eugenol (33.11%) and caryophyllene (9.29%).23 a- pinene (11.8%-15.3%), β-pinene (26.4%-43.1%), limonene (6.3%-10.6%) and β- caryophylene (5.6%-9.3%) are the main compounds in the root, stem and fruit oils of P. longum while camphene (13.9%) and bornyl acetate (10.4%) are supplementary compounds in the root. The leaf oil of P. longum restrain (E)- nerolidol (19.08%) and β-caryophyllene (12.25%) as well as (E)- nerolidol (22.5%) and β- caryophyllene (16.88%).22, 23, 24 In Vietnam species of piper, major compound identified in the leaf oil was fonenol (40.5%).24

Pharmacological Actions Analgesic Activity In a study G.vedhanayaki et.al proves that piper exhibit opioid type analgesia and NSAID type analgesia by using rat tail flick method and acetic acid writhing method. It states that Piper longum roots show weak opioid but a potent NSAID type of analgesia.2 Hepatoprotective and Antifibrotic Activity A study of A.J.M.Christina et.al shows that the ethanolic extract of Pipper longum reduced the liver injury which was produced by CCL4 administration and improved the biochemical parameters and hydroxyproline content.25 H.Rajeswary proved in rat model that a combination of extracts of Piper longum and Melia azedarach shows more potent hepatoprotectivity against CCL4 induced hepatocellular injury.26

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Antimicrobial Activity A study by M. Abbas Ali et.al stated that different types of extracts of Piper longum shows a wide range of antimicrobial activity against gram positive and gram negative bacteria but petroleum ether extract shows inhibitory effect against streptococcus aureus, ethyl acetate extract shows excellent activity against gram positive and gram negative bacteria while methanol extract shows strong activity against gram-negative Shigella flexneriae.10 P. Srinivasa Reddy showed in a study that three isolates of black pepper were active against Gram- positive bacteria and moderately active against Gram-negative bacteria. piperlonguminine active against Bacillus subtilis while piperine against Staphylococcus aureus, and pellito- rine against Bacillus sphaericus. 27

Antiamoebic Activity S.Ghoshal et.al stated in a study that ethanol extract of P. longum possessed certain antiamoebic activity in vivo while the in vitro activity was quite low. Such results, still are not uncommon with traditional remedies.28 Mast Cell Stabilizing Activity G.P. chaudhary stated in a study that ethanolic extract of Piper longum at different concentrations slow down degranulation of mast cells at a extent.29 Antigiardial Activity D. M. Tripathi et.al stated that an aqueous extract of Piper longum fruit powder and its ethanol extract shows 100% giardicidal activity.30 Immunostimulatory Activity D. M. Tripathi et.al demonstrated the immunostimulatory effect of Piper longum by some standard test parameters such as haemagglutination titre, plaque forming cell counts, macrophage migration index and phagocytic index which exhibit both specific and non-specific activity.30 Administration of alcoholic extract of Piper longum and its component piperine increased the total WBC count in mice. 31

Anthelmintic Activity

Krishnaprasad GK, et al. stated in the study that methanolic extract and fractions of Piper longum possessed potent anthelmintic activity. The chloroform fraction of P. longum possessed potent broad spectrum anthelmintic activity as it was effective against strongyle ova, larva and adult amphistomes at low IC50 values.32

Anti Alzheimer's Activity Gu. SM et.al demonstrated in the study that behavioral tests showed that Piper longum inhibited Lipopolysaccharide-induced memory. Piper longum also prevented Lipopolysaccharide -induced beta-amyloid (Aβ) accumulation and inhibited the activities of β- and γ-secretases. Piper longum therefore demonstrates potential for the treatment of Alzheimer's disease.33

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Preventing Voiding Dysfunction Da-Ae Park et.al invented in a study that extract of Piper longum may increase micturition intervals, decrease micturition pressure, increase bladder capacity, inhibit detrusor contraction and induce detrusor relaxation. 34

REFERENCES 1. Galor SW and Benzie IFF, Herbal Medicine, CRC Press, Second Edition 2011. 2. Vedhanayki G, Shastri G.V, Kuruvilla A, Analgesic study of Piper Longum Linn. Root, Indian journal of experimental biology 2003; 41:649-651. 3. Dhar ML, Dhar MM, Dhawan BN, et al. Screening of Indian plants for Biological activity, Indian Journal of Experimental Biology, 1968; 6:232. 4. Kulshreshtha VK, Shrivastava RK, Singh N, et al. A study of Central Stimulent Effect of Piper longum, Indian journal Pharmacol ,1969; 1:8. 5. Kulshreshtha VK, Shrivastava RK, Singh N, et al. analysis of Central Stimulent activity of Piper longum, Journal of research of Indian Medicine ,1971; 6:17. 6. Banga SS, Garg LC& Atal CK, Extract of Piplartine and crude extract of Piper longum on ciliary movements, Indian Journal of Pharmacology, 1964; 26:139. 7. Manoj P, Soniya EV, Benerjee NS, et al. Recent Study on well known Spice Piper longum Linn., Natural Product Radiance, 2004; 3:222-227. 8. Chauhan K, Solanki R, Patel A, et al. Phytochemical and Therapeutic Potential of Piper longum Linn, International Journal of Research in Ayurveda & Pharmacy, 2011; 2:157- 161. 9. Kumar S, Kamboj J, Suman, Sharma S, Overview for Various Aspects of the Health Benefits of Piper Longum Linn. Fruit, Journal of Acupunct Meridian Stud 2011; 4(2):134−140. 10. Ali MA, Alam NM, Yeasmin S, et al. Antimicrobial Screening of Different Extracts of Piper longum Linn, Research Journal of Agriculture and Biological Sciences, 2007; 3(6): 852-857. 11. Kirtikar KR, Basu BD, Indian Medicinal Plants, Valley Offset Printers and Publishers Dehradun, 1996; 3: 2128-2130. 12. Nadkarni KM, Indian Materia Medica, Bombay Popular Prakashan; 1989; 1: 965-969. 13. Anonymous, The Wealth of India, CSIR,New Delhi; 1992; 8: 96-99. 14. Sala AV, Indian Medicinal Plants, Orient Longman; YNM ; 4: 290-293. 15. Gani MN, Khazainul Advia, Aijaz Publishing House, New Delhi; YNM ; 2: 125. 16. Hakeem MA, Bustan ul Mufridaat, zafar book depot,New Delhi; 1999 : 117. 17. Khan MA, Muheet e Azam(urdu translation), CCRUM, New Delhi; 2014; 3: 536-537. 18. Ashraf MA, mukhzinul mufridat, Idara taraqqi urdu; New Delhi; YNM: 256. 19. Kabiruddin, mukhzinul Mufridat, Sheikh Mohd Basheer Industries Urdu Bazaar , Delhi; 1996: 178-179. 20. Anonymous, Standarisation of Single Drugs of Unani Medicine, Edition First, CCRUM, New Delhi; 1997; 3: 85-90. 21. Kabiruddin HM, Biyaz Kabir, Hikmat book Depot,Delhi, YNM ; 2: 15, 16, 21, 137. 22. Tewtrakul S, Hase K, Kadota S, et al. Fruit oil composition of Piper chaba Hunt., P. longum L. and P. nigrum L. Journal of Essential Oil Research. 2000; 12(5):603-608. 23. Md Nazrul IB, Jaripa B, Anwar MN, Volatile constituents of essential oils isolated from leaf and inflorescences of Piper longum Linn, The Chittagong University Journal of Biological Science, 2008; 3(1, 2):77-85.

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24. Hieu LD, Hoi TM, Thang TD, et al. Fonenol, the main constituent of the essential oil of the leaf of Piper longum L, American Journal of Essential Oils and Natural Products 2018; 6(1): 16-19. 25. Christina AJM, Saraswathy GR, Robert, et al. Inhibition of CCL4-Induced Liver Fibrosis by Piper longum Linn, Phytomedicine, 2006: 196-198. 26. Rajeswary H, Vasuki R, Samudram P, et al. Hepatoprotective effect of Ethanolic Extracts of Melia azedarach Linn and Piper longum Linn and their Combination on CCL4 Induced Hepatotoxicity in Rats, Indian Jounal of Experimental Biology, 2011; 49: 276-281. 27. Reddy PS, Jamil K, Madhusudhan P, et al. Antibacterial Activity of Isolates from Piper longum and Taxus baccata, Pharmaceutical Biology, 2001; 39: 236-238. 28. Ghoshal S and Lakshmi V, Potential Antiamoebic Property of the Roots of Piper longum Linn, Phytotherapy Research, 2002; 689-691. 29. Choudhary GP, Mast Cell Stabilizing Activity of Piper longum Linn, Indian J Allergy Asthama Immunol, 2006; 20(2): 112-116. 30. Tripathi DM, GuptaN, Lakshmi V, et al. Antigiardial and Immunostimulatory Effect of Piper longum on Giardiasis due to Giardia lamblia, Phytother. Res. 1999; 13: 561–565. 31. Sunila ES, Kuttan G, Immunomodulatory and antitumor activity of Piper longum Linn. and piperine, Journal of Ethnopharmacology 2004; (90) 339–346. 32. Koorse KG, Samraj S, John P, et al. Anthelmintic Activity of Fruit Extract and Fractions of Piper longum L. In vitro, Pharmacogn J. 2018; 10(2): 333-340. 33. Gu.SM et.al, Piperlongumine Improves Lipopolysaccharide-Induced Amyloidogenesis by Suppressing NF-KappaB Pathway, neuromolecular medicine, 2018; 1-16.

34. Da-Ae Park et.al, composition for preventing, treating and improving of voiding dysfunction comprising extract from Piper longum, United States Patent Application Publication 2018; 1-17.

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