Antiinaflmmatory Activity

Antiinflammatory activity was exhibited by the fruit decoction of Piper sp. in rat paw edema induced by carrageenin (Iwamoto et al. 2015; Kumari et al. 2012).

Immunomodulatory Activity

Piperinic acid, an active constituent of P. longum, decreases the number of lymphocytes (CD4+ and CD8+ T cells) and cytokine levels in sensitized Balb/C mice, while in another study, alcoholic extract of its fruits and piperine was found to be cytotoxic (Devan et al. 2007). Pipplirasayaba, an Ayurvedic preparation containing long pepper as one of its active constituents, activates the macrophages (Agrawal et al. 2000).

Anticancer Activity

Piper sp. ethanolic extract protects the cell surface and membrane integrity in hamster buccal pouch carcinogenesis induced by 7, 12-dimethylbenz[a] anthracene (DMBA) (El Hamss et al. 2003). Piperine inhibits metastasis of the B16F-10 melanoma cells and reduces the tumor nodule formation along with the reduction in collagen hydroxyproline, hexosamine and uronic acid content, and exhibits chemopreventive effects (Pradeep et al. 2002; Selvendiran et al. 2004). Apart from piperine, piplartine, another alkaloidal amide, isolated from Piper exhibits in vitro antitumor activity. Piperine exhibits antiapoptotic, antioxidative and restorative properties against mutagenic response, and it can be useful in immunocompromised conditions (Rather et al. 2018).

Antidepressant Activity

P. longum ethanolic fruit extract, piperine and piperidine possess antidepressant activity (Lee et al. 2005; Li et al. 2007), while in another in vitro study, piperine decreases the brain derived neurotrophic factor (BDNF) mRNA expression in hippocampal neurons (Lee et al. 2008).

Antiulcer Activity

Mahakasyaya, a decoction made up of ginger, Ferula asafoetida and P. longum, was reported to inhibit the gastric ulcers in rats (Agrawal et al. 2000). Piperine inhibited the gastric emptying of solids and liquids in mice which is independent of gastric acid and pepsin secretion (Bajad et al. 2001a).

Effect on Reproductive System

Pippaliyadi vati, an Ayurvedic contraceptive, a combination of P. longum fruits benzene extract and Embeliaribes berries methanolic extract, can inhibit the pregnancy of animals (Lakshmi et al. 2006; Bajad et al. 2001a). The treated female rats gave births to low-weight, smaller-size progenies (Bajad et al. 2001a). Pippaliyadi vati does not have any adverse effect on reproductive performance and postnatal development (Munshi et al. 1972). Piperine decreases the mating performance and fertility in Swiss albino mice (Munshi et al. 1972) and showed decrease in intratesticular testosterone concentration and increased serum gonadotropins level.

Bioavailability Enhancement

Piperine induces the cell membrane dynamics and permeability and synthesis of cytoskeletal proteins. The change in the cell membrane permeability enhances the permeability and bioavailability of other drugs such as diclofenas sodium, vasicine and curcumin (Atal et al. 1981; Pattanaik et al. 2006; Singh et al. 2005; Khajuria et al. 2002; Kim et al. 2009; Kim et al. 2010).

Hepatoprotective Activity

P. longum ethanolic fruit extract and piperine both inhibit liver fibrosis. Ethanolic fruit extract improves regeneration process, while piperine reduces enzymatic leakage of glutathione pyruvate transaminase (GPT) and alkaline phosphatase (AP), lipid peroxidation and depletion of glutathione-stimulating hormone (GSH) and total thiols (Manavalan and Singh 1979).

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