Chemical constituents and bioactivity of Piper sarmentosum: a mini review

Azelan, A., Taher, Z.M., Sasano, S., Ariga, T. and Aziz A.A Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia (UTM), Johor Bahru, Malaysia. Faculty of Chemical Engineering and Energy, Universiti Teknologi Malaysia (UTM), Kuala Lumpur, Malaysia. Faculty of Engineering (Chemical Engineering), Tokyo University of Agriculture and Technology Tokyo, 184-8588, Japan Faculty of Engineering (Applied Chemistry), Tokyo University of Agriculture and Technology Tokyo, 1848588, Japan


Introduction
Herbal remedies played an enormously important role in the maintenance of human health throughout the history of mankind. Over 50% of modern clinical are sourced from various plants extracts and have been employed as supplements and nutraceuticals (Bradley, 1992;Sivasubramanian and Brindha, 2014). The genus Piper, widely distributed in the tropical and subtropical region of the world, is often used as food flavouring agents, traditional medicines (Burkill, 1966) and pest control agents (Nair andBurke, 1990, Hussain et al., 2012). P. sarmentosum Roxb. (Piperaceae), locally known as kadok, is a glabrous, creeping terrestrial herb about 20 cm tall. The leaves are dark green and variable in shape and size, usually, heart shape and cordate with 2 -8 cm long petiole (Malaysian Herbal Monograph). Kadok is well known for its medicinal properties, such as its antibacterial, antiprotozoal, antioxidant, antimalarial and hypoglycaemic effects (Zaidan et al., 2005). The picture of the plant is shown in Figure 1.
In the Malay and Indonesian Archipelago, the leaves and roots of this plant are used for the treatment of toothache, fungoid dermatitis on the feet, coughing asthma, and pleurisy (Perry, 1981). In Malaysia, P. sarmentosum leaves and roots are applied to the forehead to relieve headache while its decoction is utilized to cure muscle weakness and pain in the bones (Perry, 1981). In Indonesia, P. sarmentosum rootlets are chewed with betel nut and the juice is swallowed to treat coughs and asthma. It is also chewed with ginger to treat toothache or chewed with a little nutmeg and ginger to treat pleurisy (Perry, 1981). Warmed leaves coated with coconut oil are applied to the painful chest while the finely ground leaves mixed with a small amount of water are smeared on the throat to treat coughs. In Thailand, the roots are used as carminative and stomachic (Perry, 1981) while the fruits and leaves are used as an expectorant (Pongboonrod, 1976;Rukachaisirikul et al., 2004). This review describes the chemical constituents of P. sarmentosum and its bioactivity as the significant plant of interest. In South-East Asia, the plant has been discovered, however, extensive research to develop further still limited. In Panama, researchers have been working to explore the medicinal potential of this significant plant for its ethnomedical uses and pharmacological activities as this Piperaceae family occupying fifth place in Panamanian Flora (Durant-Archibold et al., 2018). Due to great demand, scientific studies have been extensively carrying out worldwide. Most of the studies are focusing on biological activities of plant extracts, toxicology based on dosage and marker compound identification. It is believed that herbal product with known quality in terms of phytochemical profile and biological property will increase the value of the particular herbal product significantly. The information provided in this review will be of value not only for the discovery of pharmacological use in new drugs preparation but also to promote the use as the ingredients of traditional medicine.

Material and methods
The present review paper considered the literature published prior to 2020 on chemical constituent, pharmacological activities, biological activities and ethnomedicinal uses. This review considered peerreviewed research papers available at databases as Scopus, Science Direct or Google Scholar.

Extraction methods
The separation of compounds from natural products is becoming an important part for food, flavour, fragrance and pharmaceutical industries. Food industries have to deal with handling complex molecules such as chemical constituents or phytochemicals (Tiwari, 1995). Therefore, method of extraction that being employed is important to ensure the quality and quantity of the target compound. There are various methods to extract P. sarmentosum and one of them is using soxhlet apparatus (Thitima et al., 2004). Solvent extraction of solid samples, which is commonly known as solid-liquid extraction, but which should be referred to, in a more correct use of the physicochemical terminology, as leaching or lixiviation, is one of the oldest ways of solid sample pretreatment. The most outstanding advantages of conventional Soxhlet are as follows: the sample is repeatedly brought into contact with the fresh portions of the solvent, thereby helping to displace the transfer equilibrium (de Castro and Garcıá-Ayuso, 1998). P. sarmentosum also can be extracted by using reflux (Hussain et al., 2008). Reflux is a technique involving the condensation of vapours and the return of this condensate to the system from which it originated (Proestos and Komaitis, 2008).

Antioxidants
Superoxide anion (O2 -) is a toxic by-product formed by the univalent reduction of ground-state molecular oxygen (Cunningham et al., 1987). Superoxide anion and its reduction products H2O2 and •OH produce a variety of effects on tissue macromolecules and have been implicated as participants in a variety of disease states. Since superoxide anions are produced as toxic byproducts of regular biochemical and metabolic reactions in the human biological system, a daily intake of natural antioxidant superoxide scavenger could prevent oxidative damage. A study by Vimala et al. (2003) reported that methanolic leaf extracts of P. sarmentosum and possessed a natural antioxidant superoxide scavenger, Naringenin. Naringenin belongs to the flavonoid group, 4', 5, 7-Trihydroxyflavanone. The Naringenin compound showed high superoxide scavenging activity that is 75.7% (Vimala et al., 2003).
The research by Chanwitheesuk et al. (2005) towards 43 edible plants shows that the methanolic extract of the leaves P. sarmentosum contain a high level of antioxidant activity with the index of 13.0. Antioxidant activity was determined by measuring the coupled oxidation of carotene and linoleic acid, as described by Hammerschmidt and Pratt (1978). The results suggest that the antioxidant activities of these plants may be attributed to the chemical components present, especially vitamin E and xanthophylls.

Antimicrobial
Increasing awareness of hazards associated with the use of antibiotics and chemical agents has accelerated investigations into plants and their extracts as new sources of antimicrobial agents. The increasing prevalence of multidrug-resistant strains of microorganism and the recent appearance of strains with reduced susceptibility to antibiotics raises the spectre of untreatable microbial infections and adds urgency to the search for new infection-fighting strategies. The presence of the phytochemicals like flavonoids, tannins, and steroids indicates that P. sarmentosum is rich in phenol compounds. Zaidan et al. (2005) reported the antibacterial activities of methanol extracts of P. sarmentosum leaves against Staphylococcus aureus and Pseudomonas aeruginosa. The research done by Lee et al. (2014) showed the methanol extracts of P. sarmentosum Roxb give high antibacterial activities against Escherichia coli, Burkholderia sp. and Haemophilus parasuis in proportion to high amounts of total polyphenol and flavonoid. Chemical compounds such as myristicin and brachyamide B which isolated from the essential oil of P. sarmentosum exhibited strong antifungal activity against Rhizoctonia solani and Bipolaris oryzae. Additionally, Brachyamide B and piperonal also showed strong antibacterial activity against Xanthomonas oryzae (Xoo) and pv. oryzicola (Xoc) (Chanprapai and Chavasiri, 2017).
The study done by Taweechaisupapong et al. (2010) reported the antimicrobial effects of P. sarmentosum extracts on Aggregatibacter actinomycetemcomitans, an oral microbe, which was tested by the disc diffusion method showed no inhibitory zone. The methanolic fruit  Table 1. The molecular structures of the various compounds found in P. sarmentosum extract of P. sarmentosum was found to be effective as antibacterial agents against the causal agent of sheath brown rot, Pseudomonas fuscovaginae (Rahman et al., 2016). The antibacterial activity of the fruit extract against the pathogenic bacteria P. fuscovaginae was measured by the diameter of inhibition zones produced and the MIC and MBC values. The results obtained from this study suggest that the fruit extract of P. sarmentosum has a potential to be developed as a novel bactericide.

Antidepressant
Different type of extracts of P. sarmentosum have been investigated for antidepressant-like effect in mice and few parameters were evaluated in the open field test (OFT), force swim test (FST) and tail suspension test (TST). The results indicate that P. sarmentosum increased the expression of brain-derived neurotropic factor (BDNF) and effective as an anti-depressant (Qing et al., 2017).