In most of the treatment, route of administration of drugs plays an important role and may affect the achievement of the desired pharmacological action of the drugs. Herbal medicines are normally taken via an oral route of administration. However, in some of the preclinical studies to investigate the pharmacological activity of certain medicinal plants, other systemic routes of administration were used (e.g., intraperitoneal, subcutaneous). Based on our literature searches, the antinociceptive and anti-inflammatory activities of RZZ were determined using extracts administered via intraperitoneal or subcutaneous routes. Several reasons for choosing those systemic routes of administration could be suggested. Firstly, the authors tried to compare the effectiveness of antinociceptive activity of extracts with morphine (reference drug), which is clinically given via systemic administration. It is not reasonable to compare the effect of extract with that of reference drug when the extract was given orally (because it was consumed orally) while the reference drug (morphine) was given intraperitoneally. Secondly, since most of the studies were preliminary and aimed at proving the traditional claims of the particular medicinal plant, it is believed that the authors did not establish the pharmacokinetic and pharmacodynamic of the extracts yet. It is known that orally administered compounds/extracts will undergo first-pass hepatic metabolism, and to avoid this from affecting the extract activity, systemic routes of administration were chosen.
In most of the studies, in vitro assays were applied to study the extracts pharmacological activities (e.g., antiproliferative, antiplatelet aggregation, and cytotoxicity) because cell lines permit relatively efficient and economical screening for chemotherapeutic activity when compared to in vivo assay systems [63]. Although the data obtained using the in vitro assays is limited and could not be used as a reliable source to predict what will be obtained in the in vivo assays, the former still have the advantage of providing the high-throughput preliminary data in a less time-consuming manner [64]. Other than that, the in vitro studies could be used to provide information for narrowing the scope of subsequent investigations which required more comprehensive methods and were time consuming and more expensive [65].
Of all bioactive compound(s) isolated and identified from various types of extracts of RZZ, only zerumbone has been studied extensively. Zerumbone has been demonstrated to possess in vivo antinociceptive [66], anti-inflammatory [67] and antitumour [4, 68] activities. While in the in vitro studies, zerumbone has been reported to exhibit antiproliferative [69] and antiplatelet aggregation [49] activities. Zederone, isolated from the EEZZ, was suggested to contribute to the larvicidal activity of the extract [42].