Phytochemical and pharmacological review on Stephania japonica

This paper reviews phytochemical and pharmacological profiles of Stephania japonica from the databases PubMed, Science Direct and Google Scholar up to December 2018. S. japonica is a common plant, widely distributed in all over Bangladesh. Traditionally, this plant is considered as one of the important medicinal plants in the treatment of a variety of ailments, including inflammation, pain, rheumatism, cancer, bone fracture and fever. Findings suggest that S. japonica is rich in important phytochemicals, including alkaloids, steroids, saponins and fats. It is evident to possess anti-inflammatory, antioxidant, antidiarrheal, antimicrobial, insecticidal, anti-nociceptive, neuro-protective, analgesic and anti-hyperglycaemic activities. In conclusion, S. japonica may be one of the best sources of plant-based active constituents.


Introduction
Plants have been used in traditional medicine since ancient time with a reputation as efficacious remedies regardless of insufficient scientific evidence to substantiate their efficacy. The exploration of the chemical properties of the plants throughout the age was accomplished principally through careful observation, trial and error and the accidental discovery. In this process, the human race, over the centuries, has created a vast heritage of knowledge and experience on medicinal plants in different cultures and civilizations. Most of such indigenous knowledge handed down, through the ages, by oral tradition. The major portion of the present-day knowledge of the medicinal properties of the plants is thus the sum total of these observations and experience [1]. The plant Stephania japonica Linn. belongs to the family Menisperaceae, a slender wiry climber or twining shrub [2], is widely used in the traditional medicine of Bangladesh in the treatment of a wide range of diseases and disorders, including inflammation, cancer, asthma, fever, sleep disturbance, edema, and bone fracture [3,4]. Especially its leaves, are extensively used to treat different kinds of painful conditions, more specifically, the crushed leaves for body pain [4,5] and warmed leaves for rheumatism [6]. In 1982, Matsui have isolat-  Bengali/Vernacular Name: Akanadi, Nimuka, Maknadi.

Traditional Uses
Leaves and roots are bitter and astringent; used in fever, diarrhoea, urinary diseases and dyspepsia. Leaves are mounted on the abscess and kept for bursting. Leaves are macerated in a glass of water and are taken after mixing with molasses to cure urethritis.
Leaves are also given for gastritis in Khagrachari. On the other hand, tooth paste is taken for vertigo and dysentery; root tuber mixed with root juice of Flemingia stricta (Family: Leguminosae) is taken for asthma; the root paste is warmed and rubbed in hydrocele. The ethanolic leaf extract of the plant is evident to have broad spectrum anti-bacterial and anti-fungal activities [7,8].

Anti-Inflammatory Activity
The plant extract (methanol) has been found to show significant anti-inflammatory effect on egg albumin method [10]. Ahmed et al. [11] also suggested an anti-inflammatory effect of the plant.

Anti-Diarrheal Activity
S. japonica ethanol extract at dosage level 0.5, 1 and 2 g/kg decreased the gastrointestinal motility and number of feces in rats (n = 5) (Chatterjee, 1993).

Anti-Microbial and Cytotoxic Effect
Ethyl acetate soluble fraction of the S. japonica extract was

1, 5 and 10 mg solutions of plant extract (acetone fraction)
exhibited the insecticidal effect [13]. The plant is also evident to act against Callosobruchus chinensis where at dose 5 mg, it achieved 50% death of test insect [14].

Anti-Nociceptive Activity
S. japonica is evident to show analgesic effect in mice [15]. The methanolic extract of the plant at 50, 100, and 200 mg/kg was evident to show an anti-nociceptive effect in mice [9].

Neuro-Protective Activity
In a recent study, methanolic extract of the herb showed a neuroprotective effect, possibly by reducing oxidative stress, neuroinflammation and inhibiting cholinesterase activity [10].

Anti-Hyperglycemic Effect
The methanolic extract of the plant at 250 and 500 mg/kg is evident to exert an anti-hyperglycemic effect in experimental rats [16]. S. japonica mediated anti-hyperglycemic effect was also seen by Ueda et al. [17], Gregersen et al. [18] and Hossain et al. [19].

Discussion
There is a relation between oxidative stress and inflammation [20]. Phenolic natural compounds such as flavonoids possess antioxidant and anti-inflammatory activity [21]. It is well established that the first phase of formalin test reflects neurogenic pain and the late phase corresponds to inflammatory pain responses [22].
Thus, the antioxidant and anti-inflammatory responses are the best sign of probable potent S. japonica-based constituents for the traditional usages, especially in inflammation and pain. Medicinal plant extracts offer considerable potential for the development of new agents effective against pathogents that are currently difficult to treat [23]. Noxious stimuli or infection is also related to inflammation cells [20]. S. japonica mediated antimicrobial effect is also evident in scientific report (Rahman). Recent evidence indicates that cytokines (and chemokines), as well as their receptors, are involved in the pathophysiology of many inflammatory diseases including sepsis, rheumatoid arthritis atheroscloresis and asthma.
These pathological states seem to be linked with an imbalance of cytokine network and to the excessive recruitment of leukocytes to the inflammatory sites [24,25] (Young).
Because of this, the cytokine system constitutes a very interesting and promising target for the development of clinically relevant anti-inflammatory drugs. Carrageenan induced paw edema in rats is thought to be biphasic [26]. In the second phase bradykinin, protease, prostaglandin, and lysosome are released [27]. Evidence supports that various plant-derived compounds with anti-inflammatory properties exert their effects through the modulation of cytokine system [28]. For instance, flavonoids, a class of compounds widely distributed throughout the plant kingdom possess interesting anti-inflammatory action [29]. So, resulting anti-inflammatory and antioxidant effect could be assumed either as the protective effect against oxidative stress or inhibition of enzymes of prostaglandin pathway or other enzymatic path ways of inflammatory process. Further, anti-inflammatory, anti-microbial and anti-diarrheal effects of S. japonica may be linked with each other. On the other hand, anti-hyperglycaemic and cytotoxic effects of the herb indicate potential sources of anti-diabetic and anti-cancer substances in it. Generally, antioxidant and antiinflammatory effects are protective in nature [10]. Therefore, the neuroprotective capacity of the plant may be due to its antioxidant effects in different test systems [30][31][32][33].

Conclusion
S. japonica contains a number of important phytoconstituents and possesses prominent biological activities. More studies are necessary as S. japonica may be one of the best sources of phytomedicines.