Suat Cheng Tan

Oroxylum indicum (l.) Benth. ex Kurz is an edible medicinal plant found in the South and Southeast Asian regions. Local populations utilise various parts of the plant including its pendulous-sword-like fruits, night-blooming flowers, thin-papery seeds and compound leaves as sources of medicine and food. Among its numerous phytochemicals, flavonoids, particularly the baicalein, are the most abundantly found compound. The baicalein is recognised for its potent antioxidant, anti-cancer and anti-inflammatory properties, showing promises for the treatment of cancer, diabetes and cardiovascular diseases. Despite these benefits and potentials, it is dangerous to assume all the natural plant-derived compounds are non-toxic and safe for consumption without proper scientific investigation focusing on their potential chronic toxicity for long term consumption. Therefore, a literature search was conducted using selected databases, namely PubMed, ScienceDirect and Scopus, with the keyword “Oroxylum indicum” and “baicalein” to collate relevant peer-reviewed literature for critical appraisal. The retrieved articles were critically reviewed to provide a comprehensive overview of the O. indicum, covering its ethnopharmacological uses, therapeutic potentials, scientific extraction techniques and toxicological evaluation of its major phytoconstituent – baicalein, for the benefit of future research. The insights gathered here could provide a critical information and knowledge for the regulatory agencies, consumers and manufacturers interested in food and natural products derived from O. indicum, helping to mitigate the risk associated with potential misuse and ensuring safer consumption.

This study presented the green synthesis and biological properties of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using Piper ornatum leaf extract. UV–Vis spectroscopy revealed characteristic surface plasmon resonance peaks at 420–440 nm for AgNPs and ∼550 nm for AuNPs, confirming successful nanoparticle formation. Size analysis showed AgNPs were considerably smaller (4–33 nm; average 14.74 nm) than AuNPs (67–496 nm; average 263.17 nm). FTIR analysis indicated that plant compounds containing hydroxyl, carbonyl, amine, and polysaccharide groups were responsible for reducing metal ions and stabilizing the nanoparticles. When tested for antimicrobial activity, AgNPs showed dose‐dependent inhibition of both Staphylococcus aureus and Escherichia coli , with both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 6.25 mg/mL. On the other hand, AuNPs displayed no antibacterial effects. In cancer cell studies, AgNPs significantly reduced MCF‐7 breast cancer cell viability in both a dose‐ and time‐dependent manner, with half‐maximal inhibitory concentration (IC ₅₀ ) values decreasing from ∼35 at 24 to ∼18 µg/mL at 72 h. AuNPs had minimal impact on cell viability, maintaining > 80% viable cells across all tested concentrations. The selective cytotoxicity of AgNPs was further supported by their lack of toxicity toward the noncancerous breast cell line MCF‐10A. Further investigation revealed that AgNPs suppressed several cancer‐related genes ( c-Myc , Cyclin D1 , HER2 , COX-2 , and miR-622 ) and triggered changes in nuclear structure typical of cell death through apoptosis. These results demonstrated that P. ornatum extract effectively produces nanoparticles through green synthesis, with AgNPs showing particular promise for both antibacterial and anticancer applications, while AuNPs appear better suited for biocompatible applications.

Context: Tetrahydrocurcumin (THC) exhibits superior biological and pharmacological characteristics compared to curcumin, demonstrating efficacy in suppressing tumor metastasis and angiogenesis and acting as a potent preventive agent against carcinogenesis. However, its limited water solubility restricts its application in aqueous formulations. Aims: To evaluate the efficacy of a β-cyclodextrin (β-CD)-THC inclusion complex in combating colon and liver cancer in animal models. Female rats (n=24) were divided into six groups and induced with colon and liver cancer using 1,2-dimethylhydrazine (DMH). Methods: THC or the β-CD-THC inclusion complex was orally administered twice weekly for 11 weeks. Animals were euthanized, and blood serum, colon, and liver samples were collected for analysis. Results: Results indicate that the THC inclusion complex significantly reduced high dysplasia in the colon, decreased necrotic hepatocytes, and reduced central vein diameter in the liver. Moreover, it lowered serum levels of gamma-glutamyl transferase (GGT), matrix metalloproteinase (MMP)-2, and MMP-9 in cancer-induced rats, highlighting enhanced anticancer properties when THC is complexed with β-CD. Conclusions: These findings underscore the potential of the β-CD-THC inclusion complex as a promising therapeutic strategy against colon and liver cancer.

Purpose: To investigate the therapeutic potential of baicalein-enriched fraction (BEF) extracted from Oroxylum indicum leaves on ischemic stroke in rat models induced with endothelin-1 (ET-1). Methods: A total of 10 male Sprague Dawley rats were randomly assigned to the study (n = 5) and control (n = 5) groups. Study group received 50 mg/kg BEF treatment via oral gavage administration for 4 days prior to the induction of ischemic stroke using ET-1, while control group (n = 5) received normal saline. Neurological deficits, total infarct volume, histological scoring and expression of targeted genes were evaluated. Results: The study group exhibited significantly improved motor function test, motor coordination and balance test, motor asymmetry test, and contralateral sensory test (p < 0.05) compared to control group. However, the reflex test was not significantly different between the study and control groups (p > 0.05). Furthermore, infarct volume, infarction area, and relative mRNA GABRA 6 expression were significantly lower in study group compared to control group while the relative mRNA expression of JAKMIP 1 was significantly higher (p < 0.05). Conclusion: Baicalein-enriched fraction (BEF) extracted from O. indicum leaves improves motor coordination, lowers infarction parameters and therefore, may be a potential therapeutic agent for future clinical approaches to treat ischemic stroke disease.

In recent years, numerous studies have discovered the potential of natural compounds extracted from medicinal plants as a promising alternative treatment for ischemic stroke (IS). Oroxylum indicum is among the plants that has been widely proven to contain a beneficial flavonoid compound known as baicalein. However, the therapeutic potential of this compound for IS disease has yet to be demonstrated. In this study, a baicalein-enriched fraction (BEF) was harvested from the leaves of O. indicum and tested on neural stem cells (NSCs) to determine its effects on the cell viability and gene expression prior to an in vivo animal study. NSCs were chosen because they are the primitive brain cells that play important roles in neurogenesis after IS injury. It was found that NSCs treated with BEF at concentration of 3.125 µg/mL for 48 hours showed a significant higher cell proliferation rate. Moreover, these cells expressed high NSC markers (Nestin and SOX2) and genes responsible for antioxidant (SOD2) and angiogenesis (ANGPT1) mechanisms, indicating that the BEF treatment could enhance the progenitor brain cells viability and the expression of cytokines that are beneficial to reduce oxidative stress and reinstate blood flow in an ischemic brain. Subsequently, the in vivo therapeutic effects of BEF for IS disease was tested by administering 50 mg/kg b.wt of BEF to male Sprague Dawley (SD) rats via oral gavage before and after induction of IS. Assessments of neurological impairments were performed using a modified neurological severity score (mNSS) and the quantification of the total infarct volume was evaluated as the endpoint of this study. Results showed that an oral administration of BEF improved the behavioral scoring for motor functions (forelimb flexion and forelimb twisting), contralateral sensory functions (paw-whiskers test), motor coordination, balance functions (beam balance test) and reflex functions (pinna, corneal, startle and tail reflex) within 24–72 h; alternatively, the non-treated rats showed continuously lower scores for all the tests throughout the study, indicating that the BEF-treated rats exhibited a faster recovery rate as compared to the non-treated rats. Such improvements were observed up to two weeks. In addition, histological assessment also revealed a reduction of infarct volume in the BEF-treated rats as compared to the control rats. In summary, the present study demonstrated the potential of BEF extracted from the O. indicum as a supplement to improve preclinical IS models.

Biomaterial application strategies to enhance stem cell-based therapy for ischemic stroke

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 ([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.