In Southeast Asia, traditional medicine has a longestablished history and plays an important role in the health care system. Various traditional medicinal plants have been used to treat diseases since ancient times and much of this traditional knowledge remains preserved today. Oroxylum indicum (beko plant) is one of the medicinal herb plants that is widely distributed throughout Asia. It is a versatile plant and almost every part of the plant is reported to possess a wide range of pharmacological activities. Many of the important bioactivities of this medicinal plant is related to the most abundant bioactive constituent found in this plant—the baicalein. Nonetheless, there is still no systematic review to report and vindicate the biological activities and therapeutic potential of baicalein extracted from O. indicum to treat human diseases. In this review, we aimed to systematically present in vivo and in vitro studies searched from PubMed, ScienceDirect, Scopus and Google Scholar database up to 31 March 2020 based on keywords “Oroxylum indicum” and “baicalein”. After an initial screening of titles and abstracts, followed by a full-text analysis and validation, 20 articles that fulfilled all the inclusion and exclusion criteria were included in this systematic review. The searched data comprehensively reported the biological activities and therapeutic potential of baicalein originating from the O. indicum plant for anti-cancer, antibacterial, anti-hyperglycemia, neurogenesis, cardioprotective, anti-adipogenesis, anti-inflammatory and wound healing effects. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of this natural active compound in human clinical studies. In conclusion, this systematic review article provides new insight into O. indicum and its active constituent baicalein as a prospective complementary therapy from the perspective of modern and scientific aspect. We indicate the potential of this natural product to be developed into more conscientious and judicious evidencebased medicine in the future. However, we also recommend more clinical research to confirm the efficacy and safety of baicalein as therapeutic medicine for patients.

Glioblastoma multiforme (GBM) is the most malignant subtype of primary brain cancer. To date, standard clinical treatment for GBM is limited in effectiveness and could impose additional side effects. Recently, numerous bioactive compounds isolated from natural plants appear to have beneficial anti-cancer properties. Here, the GBM inhibitory effect of baicalein, a bioactive flavonoid extracted from Oroxylum indicum (L.) Benth. ex Kurz, was evaluated. Firstly, three solvents were used to extract the baicalein. We found that the binary extraction system, using a combination of petroleum ether and methanol (PM), yielded the highest amount of baicalein (15%) compared to the mono extraction system using methanol (13%) or aqueous (0.04%) only. In order to further enhance the baicalein yield in PM crude extract, it was subjected to an enrichment fractionation procedure, which successfully increased the baicalein by nearly two-fold from the initial crude extract (15%) to the enriched fraction 5 (F5) (29%). The enriched F5 not only showed significantly higher (~2.5-fold) antioxidant properties as compared to the crude extract, it was also found to significantly suppress GBM cell proliferation ~2.5-fold better than the crude extract. In conclusion, this study successfully optimized an extraction procedure for increased yield of baicalein metabolite from O. indicum leaves and enhanced its therapeutic potential for GBM treatment.

In recent years, herbal medicine has experienced rapid development in the search for alternative anticancer compounds. Various phytochemicals present in Quercus infectoria (QI) galls have been reported to trigger cytotoxic effects on many types of cancer cells. However, a specific active constituent of QI galls with the potential to inhibit highly invasive stage IV malignant brain tumor, glioblastoma multiforme (GBM), is yet to be discovered. In this study, a two-phase system composed of aqueous soxhlet extraction and methanolic enrichment fractionation was employed to extract an anticancer compound, gallotannin, from the QI galls. This optimized two-phase system successfully generated a fraction (F4) with ~71% gallotannin, verified by the TLC and HPLC assays. Astoundingly, this fraction showed significantly higher (~1.15-fold) antioxidant activities compared to its crude extract, as well as to a commercial synthetic pure gallotannin. The F4 was also found to significantly suppress GBM cell growth, better than the synthetic pure gallotannin and the QI gall crude extract, probably related to its significantly higher antioxidant property. Moreover, the inhibitory effects exerted by the F4 treatment on GBM cells were comparable to the effects of two clinically used chemo-drugs (Temozolomide and Tamoxifen), indicating its high efficiency in combating human cancer. In conclusion, this study pioneered the development of an optimized extraction procedure for enriched yield of the natural gallotannin metabolite from the galls of the QI medicinal plant with high antioxidant potential and inhibitory effects on human GBM cells.

The main constituents found in QI gall are tannins (50%-70%) with a small amount of free gallic acid and ellagic acid. 6 Furthermore, QI gall also is found to contain trace amount of beta-sitosterol, amenoflavone, hexamethyl ether, isocryptomerin, calcium oxalate, methyl oleanolate, as well as gum, sugar and essential oil. 7 Being the most abundantly found active compound in QI gall, tannins are believed to play significant role in the bioactivities of the QI plant. Thus, the recovery of tannins compounds from QI is particularly of interest in this study.Tannins are a group of polyphenols that are naturally found in a variety of edible plants, including tea 8 , most berries 9 such as strawberries, cranberries, blueberries and in some grapes. 10 Tannins in these plants serve as a natural defence mechanism against pest attack or microbial infections. 11 Tannins also have been reported to exert other physiological effects, such as to accelerate blood clotting, reduce

Stroke is a cerebrovascular disease, contributing to major morbidity and mortality worldwide, with significant clinical and socioeconomic burdens [1]. In Malaysia, stroke is ranked as the third leading cause of death after ischemic heart disease and pneumonia with an alarming rising trend [2]. There are two major types of strokes, namely ischemic stroke (IS) and haemorrhagic stroke. IS caused by thromboembolic occlusion of cerebral artery is the main type of stroke in Malaysia, in which it is comprised up to two-third of total reported stroke cases, as compared to the haemorrhagic stroke [3]. Main pathological events of brain ischemia include a series of biological reactions such as oxidative stress, inflammatory cytokine release, and ischemic-reperfusion injury, leading to cell apoptosis and irreversible neurological damage [4]. Up to date, recombinant tissue plasminogen activator (rt-PA) is still the gold standard drug approved by Food and Drug Administration (FDA) for the clinical treatment of IS [5]. However, due to its narrow therapeutic window (<4.5h), high re-incidence rate and short half-life (<5 min) [5], the application of rt-PA is limited [6]. Therefore, many researchers are exploring other therapeutic approaches to tackle this disease.    In recent years, increasing evidences have discovered the potential of natural compounds extracted from plants as a promising alternative strategy against IS. Among the potential plant that possess blood-brain barrier properties, an important characteristics as neuroprotective agent for neurological disorder is Oroxylum indicum [6]. It has been reported that O. indicum has a dominant active compound, namely as baicalein that are responsible in this plant’s biological activities [7]. Therefore, in this study, we aimed to evaluate the potential of baicalein extracted from the leaves of Oroxylum indicum to treat the diseases. Briefly, 10 male Sprague Dawley rats were used in this study (n=5). 50 mg/kg b.wt of baicalein was orally administered via oral gavage before and after induction of ischemic stroke by endothelin-1 (ET-1), while control group was given normal saline. Assessments of behavioral scoring using modified neurological severity score (mNSS) and infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining were evaluated as the endpoint of this study.   Results demonstrated that the oral administration of baicalein improved the behavioral scoring of rats in motor test (forelimb flexion and forelimb twisting), contralateral sensory test (paw-whiskers), motor coordination and balance function and reflex test (pinna, corneal, startle and tail reflex) within 24 h -72 h, indicating that the baicalein-treated rats exhibited faster recovery rate as compared to non-treated rats (Figure 1A-D). Such improvements were observed up to two weeks. In addition, histological assessment using TTC staining also revealed reduction of infarct volume in baicalein-treated rats as compared to control rats. However, the percentage of infarct volume to whole brain was not significantly different in both groups (Figure 2). The promising results displayed by baicalein might be contributed by its anti-inflammatory property. Several studies reported that baicalein, a type of flavonoid compound, are responsible in attenuation of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage and inhibit NF-kB activation [7,8]. LPS is the potent macrophage activator, while NF-kB is a transcription factor that can cause inflammatory cytokines release in various cell types [9, 10]. In summary, the present study demonstrates that oral administration of baicalein in ischemic stroke rats could be effectively addressed and improved behavioral scoring in treated rats as early as 24 h after baicalein treatment.