Piper longum L.

Last updated: 01 December 2016

Scientific Name

Piper longum L.

Synonyms

Chavica longa H.Karst., Chavica roxburghii Miq., Chavica sarmentosa Miq., Piper roxburghii (Miq.) J.Presl. [1]

Vernacular Name

Malaysia Bakek, chabai, kadok, sireh kadok [2]
English Indian long pepper, long pepper [2]
China Bi ba, pi po [2]
India Akaci, akari, alakalunku, alakuman, amirtai, amirutai, ampinati, ampu, arakanti, arake, argadi, aricitip-pili, arippalam, arisi thippili, ariyantipilli, ariyapalam, ari-yappalam, arkali, arkati, arke, arkki, arsithipilli, arttikam, atcatti, ati maruntu, atimaruntu, atti, attikatiyam, bithi-paukang, calani, calini, camilaki, camilakikam, camivaci, canam, capala, capalai, capalatikam, caram, catalam, cat-evi, cati, catikam, catikasira, cattu-tirpali, cattutirpali, cau-canti-caunti, cauntikam, cavikam, cavuntai, cavuntakam, cavuntam, cavunti, cavvantam, cayalati, cayini, cayinikam, cayulati, cayutai, cemmai, ceruppatai, chanchala, Chapala, chupula, cilerpananaci, cilettumanaci, cilettumanacini, cilettumattukkati, cincitai, civalokatti, cukkumatantulam, cukkumattantulam, cuttaterpati, dantakapha, dar-filfil, dar filfil, ekalakikam, ekam, ekavacam, farpipar, filfil-i-daraz, filfilderaz, gomanika, granthika, granthikam, hipli, hippali, hippali balli, inkai, ippali, irattai, kagophale, kakari, kakattiruppi, magadha, magadhaja, magadhajam, naruk-kuttippili, narukkuveru, natikantai, osanam, palappiratikam, palappiratitam, palappiretam, rali, rally, ratintikam, sadgraathi, sadgranthi, sarvagranthikam, takkolam, tandula, tanman, ulakulam, ulavainaci, uncaram, vaidehi, vaidehikana, vaitaki, yippali [2]
Lepcha Kuntim paot [2]
Nepal Pipi, pipla [2]
Sanskrit Pippali [2]
Tibetan Dorsman, drosman narmo, na-le-sam, pi-pi-ling, pi pi lin, pi pi lin gi rsta ba [2]
Indonesia Chabi-jawa [3]
France Poiure longue [3]
Spain Primieta larag [3]
Italy Pepe lungo [3]
Germany Langer pffer [3].

Geographical Distributions

Piper longum is a found in southern and eastern India. It is cultivated elsewhere and is usually planted as an attractive pot plant. [4]

Botanical Description

P. longum is a member of the Piperaceae family. [1]

The stem is shrubby and climbing.

The lower leaves are ovate-cordate with three to five-nerved; the upper ones are on short petioles, oblong, acuminated, oblique, and somewhat cordate at the base, obsoletely found five-nerved and veined, coriaceous, smooth, greyish-green beneath. Penducles are longer than the petiole. Spandix is almost cylindrical. [5]

Cultivation

No documentation.

Chemical Constituent

The root of P. longum has been reported to contain alkaloid compounds (e.g. piperlongumine and piperlonguminine). [6]

The fruit of P. longum has been reported to contain dehydropipernonaline, [7] piperlongiminine, piperine, and pipernonaline [8].

Plant Part Used

Dried fruits, roots, and stems [3][9][10]

Traditional Use

In the alimentary tract, P. longum aids in improving appetite, relieves abdominal distension and colic. It helps relieve diarrhoea and dysentery while at the same time relieves constipation. In East Asia the fruit is used to treat nausea and vomiting, epigastic pain and acute gastroenteritis. [11][12]

In India the dried fruit is used in remedies for cough, hoarseness of voice and asthma. For this purpose, they prescribed the powdered fruit in honey. Another remedy which addresses catarrh and hoarseness of voice is a combination of P. longum fruit, black pepper and ginger in equal portions. When the fruit is mixed with black pepper, ginger, cinnamon and caraway they act as an expectorant. On the other hand for dry cough, equal parts of P. longum, round zedoary, ginger, root of Clerodendron siphonanthus and raisins is a very useful remedy given in doses of 30 grains with honey or treacle. [9]

The Hindus highly prized the roots of long pepper as it possesses similar qualities as the fruit, and is prescribed in cases of palsy, tetanus and apoplexy. P. longum and black pepper form part of several irritating snuff used in coma and drowsiness. It is also used in insomnia. The oil prepared with P. longum in it is used to treat sciatica and paraplegia. [3][9]

Other uses of P. longum include the treatment of fever, inflammation, urinary discharges, leprosy and tuberculous glands. The root and fruit in combination is good for gout and lumbago. Infusion of the roots is prescribed after delivery to induce the expulsion of placenta. [11]

In Ayurvedic medicine, P. longum is most commonly known for its benefits in the respiratory and digestive systems. In the Caraka Samhita, one of the three ancient texts on which Ayurveda is based, P. longum is qualified as preventative in asthma. [10]

P. longum, alone, is also considered useful in the treatment of arthritis and sciatica. [10]

Preclinical Data

Pharmacology

Hepatoprotective activity

Piperine is an active alkaloidal constituent of extract of P. longum has been reported to exhibit hepatoprotective ability and significant protective effects against liver damage was due to its ability to reduce the lipid peroxidation and enzymatic leakage of GPT and AP and by preventing the depletion of GSH and total thiols in the intoxicated mice. Piperine showed lower hepatoprotective potency than silymarin. [13]

Ethanolic extract of P. longum has been reported to reduce the hydroxyl proline and other serum enzyme parameters for liver damage. It has been noticed that the deposition of collagen was also reduced. This shows that the extract could inhibit liver fibrosis induced by CCl4. [14]

Antifertility activity

An ayurvedic contraceptive containing equal parts of powdered seeds or fruit berries of Embelia ribes, fruit of P. longum and borax was the subject of scrutiny by Chaudhury [15] reported the effect on foetal birth weight and length after administration of the drug. The birth weight and length were lower than those of control group.

The ayurvedic contraceptive pippaliyadi yoga has been reported on postnatal development toxicity and reproductive performance of the progeny exposed to the drug in utero. They found that the drug did not possess any significant effects on the postnatal development and reproductive performance of the progeny. [16]

The crude extract of P. longum and its hexane fraction has been reported to exhibit antifertility effects in female rats. [17]

Antiulcer activity

The water extract of P. longum was found to have significant gastric ulcer protective properties when rats were given 50 mg/kg orally 60 minutes prior to subjecting them to ulreogenic activities including cold restrained stress, aspirin (200 mg/kg, 4hrs) and 4 hr pylorus ligation did not develop gastric ulcer. It seems that this effect is due to the augmentation of mucin secreting and decreased cell shedding rather than offensive acid and pepsin secretion. [18]

Antihyperlipidaemic activity

Jin [8] found that piperlonguminine, piperine and pipernonaline isolated from ethanol extract of the fruit of P. longum were the main antihyperlipidaemic constituents. Their activity is comparable to those of simvastatin.

Bioavailability of drugs activity

Atal [19] studied the effects of giving P. longum in combination with vaccine and sparteine in an attempt to determine whether it would affect the bioavailability of the drug. They found that the extract could increase blood levels of vasicine by nearly 233% while piperine in particular increased the blood levels of sparteine by more than 100%. The probable mechanism is by promoting rapid absorption from gastrointestinal tract, or by protecting the drug from being metabolized in its first passage through the liver or by a combination of both.

Khajuria [20]  suggested that piperine from P. longum may induce alterations in membrane dynamics and permeation characteristics, along with inducing the synthesis of protein associated with cytoskeletal functions, resulating in an increase in the small intestinal absorptive surface, thus assisting efficient permeation through the epithelial barrier.

Anti-inflammatory activity

The dried fruit oil of P. longum exhibited significant anti-inflammatory activity in rats using the carrageenan-induced right hind paw edema method.   The results indicated that the dried fruit's oil produced significant (p < 0.001) antiinflammatory activity when compared with the standard and untreated control. [21]

Singh et al [22] showed that the P. longum chloroform extract expressed the anti-inflammatory activity by inhibiting adhesions of neutrophils to endothelial monolayer by blocking the TNF-alpha-induced expression of CAMs i.e. ICAM-1, VCAM-1 and E-selectin through inhibition of NF-kappaB in endothelial cells.

Piperine that isolated from P. longum extract has been reported to exhibit antioxidant activity which further contributes to the anti-inflammatory activity. Piperine expressed its anti-inflammatory activity through inhibition of LPS-induced endotoxin shock via inhibition of 1 IFN production. [23]

Ethyl 3‘,4‘,5‘-trimethoxycinnamate and piperine isolated from hexane and chloroform extracts of P. longum has been reported to exhibit anti-inflammatory activity. Both compounds inhibited the TNF-α-induced expression of ICAM-1 in a dose- and time-dependent manner. [24]

Antiplatelet aggregation activity

The ethanol extract of P. longum has been reported to inhibit platelet aggregation as a non-competitive thromboxane A(2) receptor antagonist. They subsequently isolated a compound piperlongumine which proved to be a thromboxane A(2) receptor antagonist. [25][26]

Park [27] found that three other acidamides (piperine, pipernonaline and piperoctadecalidine) isolated from the fruit of P. longum also has similar effects but not as strong as piperlongumine.

Park et al [28] further used piperlongumine as the lead compound to synthesize seven other derivatives with anti-platelet aggregation activities (1-piperidin-1-yl-3-(3,4,5-trimethoxy-phenyl)prop-2-en-1-one, 1-morpholin-4-yl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, 1-(2-methylpiperidin-1-yl)-3-(3,4,5-tri-methoxyphenyl)prop-2-en-1-one, 1-(3-hydroxypiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)- prop-2-en-1-one, 1-[3-(3,4,5-tri-methoxyphenyl) acryloyl]-piperidin-2-one and ethyl 1-[3-(3,4,5-trimethoxyphenyl)-acryloyl]piperidine-4-carboxylate.

Analgesic activity

Vedhanayaki [29] reported some analgesic activity in the root extracts of P. longum. Their studies indicated that the root has weak opoid but potent NSAID type of analgesic activity.

MAO Inhibitior and Antidepressant activity

Lee et al [30][31] studied the MAO and Anti-depressant activity of P. longum extracts. They isolated three compounds which showed activity against MAO and also anti-depressant activity. These compounds are piperine, methylpiperine and guineensine.

Anti-melanogenesis activity

Piperlonguminine isolated from P. longum has been reported to possess an inhibitory effect on alpha-melanocyte stimulating hormone-induced melanogenesis. This effect is by an inhibitory effect on alpha-MSH-induced tyrosinase synthesis. This effect was through inhibiting the alpha-MSH-induced signalling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia-associated transcription factor which is a key activator of the tyrosinase promoter. [32][33]

An ethanol extract of fruits of P. longum was found to exhibit a potent inhibitory effect against alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led to the isolation of prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These compounds and the crude extract of the fruits of P. longum may have suppressive effects against pigmentation by melanin in the skin. [34]

Antioxidant activity

Piperine, an alkaloid is a major component of the fruit of P. longum has been demonstrated to exhibit antioxidant activity. It was found that it could lower the TNF-alpha levels in lipopolysaccharide and concanavalin-A stimulated animals. It also reduced the nitrite level in Concanavalin-A and lipopolysaccharide treated animals. [35][36]

Methanolic extract of fruits of P. longum has been reported to exhibit anti-oxidative activity that could reduce the cardiotoxicity effects of adriamycin (ADR). P. longum extract 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 21st day showed showed significant decrease in the activities of marker enzymes aspartate transaminase, alanine transaminase, lactate dehydrogenase and creatine kinase in heart with a concomitant increase in their activities in serum. [37]

Ethanol extract of fruits of P. longum has been reported to reduce the oxidative stress induced by monosodium glutamate. Oral administration of ethanol extract of P. longum at 300 mg/kg body weight along with MSG significantly reduced the levels of lipid peroxides in serum, liver and kidney, serum AST activity, serum levels of triacylglycerol and total cholesterol. [38]

Cytotoxic activity

Alcoholic extract of the fruits of P. longum and its component piperine has been reported to exhibit immunomodulatory and antitumor activity. 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. [39]

Apart from affecting the cell viability, piperine showed chemopreventive activity. Selvendiran [40] showed that piperine enhanced the detoxification enzyme system and reduced DNA damage. Thus it played a role in the prevention of carcinogenesis.

Again Selvendiran [41] showed that the chemopreventive effect can also be attributed to its ability to increase the activities of mitochondrial enzymes suggesting its role in motichondiral energy production.

In another study, Selvendrian [42] found that the chemopreventive activity could also be through modulation of protein bound carbohydrate levels as they are one of the markers of tumorigenesis.

Piperine also has been reported to inhibit lung metastasis induced by B16F-10 melanoma cells in mice. Simultaneous administration of the compound with tumor induction produced a significant reduction (95.2%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of the control animals compared to normal animals (0.95 microg/mg protein) was significantly reduced (2.59 microg/mg protein) in the piperine-treated animals. [43]

Extract of P. longum has been reported to exhibit antiangiogenic activity using in vivo and in vitro models. Result obtained show that intraperitoneal administration of the extract (10 mg/dose/animal) significantly inhibited (50.6%) the number of tumor-directed capillaries induced by injecting B16F-10 melanoma cells on the ventral side of C57BL/6 mice. [44]

Radioprotective activity

The ethanol extract of P. longum showed radioprotective activity as evidenced by the following changes seen in animal treated with the extract prior to irradiation. 1. The white blood cell count was 2783.3 cells/mm3 after 3 days as compared to 1900 cells/mm3 in untreated animals. The extract enhanced the number of bone marrow cells and alpha-estrase positive cells. 3. The extract reduced the elevated levels of glutathione pyruvate transferase, alkaline phoshatase and lipid peroxidation and increased the reduced glutathione production. [45]

Antiamicrobial activity

Aqueous and ethanol extract of fruits of P. longum has been demonstrated to exhibit antigiardial activity. Result obtained show that aqueous extract of P. longum at 250 μg/mL and its ethanol extract at 125 μg/mL showed 100% giardicidal activity. [46]

Ghoshal [47][48] found that extracts of the fruits and roots of P. longum is effective against Entamoeba histolytica infection in rats. Piperine was found to be the compound responsible for this activity. Sawangjaroen [49] also found similar effects of crude methanol extract of P. longum fruit against E. histolytica infecting the caesum of mice. Other protozoa affected by P. longum include Blastocytis hominis, [50] Fasciola gigantic, [51] and Leishmania donovani [52].

Pippali rasayana, an Ayurvedic herbal medicine, prepared from P. longum and Butea monepserma has been reported to exhibit antigiardial and immune-stimulatory activity in mice. Results showed that it produced up to 98% recovery from the infection. The rasayana had no killing effect on the parasite in vitro. It induced significant activation of macrophages as evidenced by increased macrophage migration index (MMI) and phagocytic activity. [53]

Toxicity

No documentation.

Clinical Data

Clinical findings

Yamada [54][55] studied that effects on taking P. longum capsules on women complaining of chills. A skin surface temperature recording every minute for 11 minutes showed that P. longum significantly facilitated the recovery of skin surface temperature at both low and high doses.

In a clinical trial conducted by Pattanaik [56] they found that by adding active compound of P. longum, piperine 20 mg along with phenytoin there was an increase in the mean plasma concentration of phenytoin at different time points (0, 0.5, 1, 2, 4, 6, 9, 12 hr.) This shows that piperine acts in similar manner in humans as in animal studies cited above, i.e. it enhances the bioavailability of drugs when given in combination.

Pippali rasayana, an Indian ayurvedic drug prepared from P. longum and Butea monosperma was administered at a dose of 1 g p.o. three times daily for a period of 15 days to patients (25 treated, 25 placebo controls) suffering from giardiasis with clinical signs and symptoms, and stools positive for trophozoites/cysts of Giardia lamblia. After 15 days of drug treatment there was a complete disappearance of G. lamblia (trophozoites/cysts) from the stools of 23 out of 25 patients. [57]

A 1980 study of asthma in children age 1 to 12 found P. longum to greatly reduce both the severity and frequency of asthmatic incidents. The study consisted of 240 children all suffering from asthma, taking increasing doses of the powdered fruit two to three times a day,  starting at from as little as 1g per dose to a maximum of 30g per dose. Once the maximum dosage was reached, each successive dose contained decreasing amounts of P. longum until the original dosage level was reached.  The results of this treatment dramatically reduced the symptoms of asthma in nearly 80 percent of the subjects. Those of the majority found that asthmatic symptoms not only occurred less frequently, but with significantly decreased severity. A small minority of 8 percent, however, found that their symptoms were aggravated after the treatment. [58]

Precautions

No documentation.

Interaction & Depletion

No documentation.

Contraindications

No documentation.

Dosage

Dosage Range

500–1000 mg per day of crude dried herb of P. longum one to three times per day.

To prepare the infusion of the herb, begin with 3 peppers at one dose with honey, increasing by 3 long peppers per day until the dosage reaches 30 per day. [59]

Most Common Dosage

No documentation.

Standardisation

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

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