Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health-promoting activities.

Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.

Betelvine (Piper betle L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes.

Piper betle L. (synonym: Piper betel Blanco), or betel vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as the green gold. The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart-shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes of P. betle are antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application of P. betle did not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety of P. betle. The findings suggest that P. betle represents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure-activity relationships, bioavailability and synergistic interactions with other drugs.

Biotechnology for propagation and secondary metabolite production in Bacopa monnieri.

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri.

Unravelling the multi-faceted regulatory role of polyamines in plant biotechnology, transgenics and secondary metabolomics.

Polyamines (PAs) are ubiquitous low-molecular-weight, aliphatic compounds with wide as well as complex application in fundamental areas of plant growth and development. PAs are mediator of basic metabolism of organisms which include cell division and differentiation, biotic and abiotic stress tolerance, reversal of oxidative damage, stabilization of nucleic acids, and protein and phospholipid binding. In plants, it attributes in direct and indirect organogenesis, endogenous phytohormone regulation, cellular compartmentalization, fruit and flower development, senescence, and secondary metabolite production which are highly tuned as first line of defense response. There are several aspects of polyamine-directed mechanism that regulate overall plant growth in vitro and in vivo. In the present review, we have critically discussed the role played by polyamine on the enhanced production of bioactive natural products and how the same polyamines are functioning against different environmental stress conditions, i.e., salinity, drought, high CO2 content, herbivory, and physical wounding. The role of polyamines on elicitation process has been highlighted previously, but it is important to note that its activity as growth regulator under in vitro condition is correlated with an array of intertwined mechanism and physiological tuning. Medicinal plants under different developmental stages of micropropagation are characterized with different functional aspects and regulatory changes during embryogenesis and organogenesis. The effect of precursor molecules as well as additives and biosynthetic inhibitors of polyamines in rhizogenesis, callogenesis, tuberization, embryogenesis, callus formation, and metabolite production has been discussed thoroughly. The beneficial effect of exogenous application of PAs in elicitation of secondary metabolite production, plant growth and morphogenesis and overall stress tolerance are summarized in this present work. KEY POINTS: • Polyamines (PAs) play crucial roles in in vitro organogenesis. • PAs elicitate bioactive secondary metabolites (SMs). • Transgenic studies elucidate and optimize PA biosynthetic genes coding SMs.

Anticancer Potential of Aqueous Ethanol Seed Extract of Ziziphus mauritiana against Cancer Cell Lines and Ehrlich Ascites Carcinoma.

Ziziphus mauritiana (Lamk.) is a fruit tree that has folkloric implications against many ailments and diseases. In the present study, anticancer potential of seed extract of Ziziphus mauritiana in vitro against different cell lines (HL-60, Molt-4, HeLa, and normal cell line HGF) by MTT assay as well as in vivo against Ehrich ascites carcinoma bearing Swiss albino mice was investigated. The extract was found to markedly inhibit the proliferation of HL-60 cells. Annexin and PI binding of treated HL-60 cells indicated apoptosis induction by extract in a dose-dependent manner. The cell cycle analysis revealed a prominent increase in sub Go population at concentration of 20 µg/ml and above. Agarose gel electrophoresis confirmed DNA fragmentation in HL-60 cells after 3 h incubation with extract. The extract also exhibited potent anticancer potential in vivo. Treatment of Ehrlich ascites carcinoma bearing Swiss albino mice with varied doses (100-800 mg/kg b.wt.) of plant extract significantly reduced tumor volume and viable tumor cell count and improved haemoglobin content, RBC count, mean survival time, tumor inhibition, and percentage life span. The enhanced antioxidant status in extract-treated animals was evident from decline in levels of lipid peroxidation and increased levels of glutathione, catalase, and superoxide dismutase.

Hypoglycemic activity of Ziziphus mauritiana aqueous ethanol seed extract in alloxan-induced diabetic mice.

Ziziphus mauritiana Lamk. (Rhamnaceae) is a fruit tree that has been used as folkloric medicine for many ailments and diseases. In the present study, the hypoglycemic effect of seed extract of Ziziphus mauritiana in alloxan-induced diabetic mice was assessed. Seed extract was administered orally at doses of 100, 400, and 800 mg/kg body weight (bw) and also in combination with glyburide (800 mg/kg seed extract and 10 mg/kg glyburide) to different groups of mice (normal and alloxan-treated diabetic mice). Their blood glucose level (in acute and sub-acute study), body weight, and mortality rate were monitored. Oral glucose tolerance test (OGTT) was also performed. Oral administration of extract alone or in combination with glyburide reduced the blood glucose level in all the diabetic mice after acute and sub-acute (28 days) administration. Administration of the extract reduced the weight loss and mortality rate during the sub-acute study. The results of blood glucose level, loss in body weight, and mortality rate were more pronounced in the group treated with combination (800 mg/kg seed extract and 10 mg/kg glyburide). The extract also augmented the glucose tolerance in both normal and diabetic mice. These results suggest that the extract possesses synergistic hypoglycemic activity.

Augmentation of expression of immunocytes' functions by seed extract of Ziziphus mauritiana (Lamk.).

AIM OF THE STUDY: The present study was carried out to evaluate the immunomodulatory potential of Ziziphus mauritiana (Lamk.) seed extract to ascertain the folkloric claim as immunomodulator. MATERIALS AND METHODS: The aqueous-ethanolic seed extract (100-400 mg kg(-1)) of Z. mauritiana was investigated for immunomodulatory potential in mice. The extract was standardized with HPLC using betulinic acid as a marker. Functions of various immunocytes in the form of humoral (development of anti-SRBC (sheep red blood cells) antibody titers) and cell-mediated immune response (delayed type hypersensitivity, nitroblue tetrazolium reduction, inducible nitric oxide synthase activity and bactericidal activity) was studied in SRBC immunized mice. The cytokine, IFN-gamma (interferon-gamma) and IL-4 (interleukin-4) secretion was also measured quantitatively by ELISA as the expression of functions of Th-1 and Th-2 respectively. Levamisole (2.5 mg kg(-1)) was used as standard drug. RESULTS: The seed extract demonstrated significant (P<0.05-0.001) up-regulation of cell-mediated, humoral immune response and Th-1 mediated cytokine IFN-gamma and decline in Th-2 mediated cytokine IL-4. At higher dose of extract the results were comparable to that of the levamisole. CONCLUSION: The immunostimulatory potential of this seed extract is likely to be mediated through its effect on macrophage function and Th-1 mediated immunity confirming the folkloric use of this plant.