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  1. Yam MF, Tew WY, Tan CS, Qiu Q, Zhou R, Wang X, et al.
    Hypertens Res, 2024 Nov;47(11):3193-3199.
    PMID: 39300303 DOI: 10.1038/s41440-024-01907-0
    Modern medicines often follow a "single-compound, single-target" paradigm, which may not be effective against complex diseases with multifactorial causes. Medicinal plants, such as Orthosiphon stamineus-widely used in Southeast Asia for its significant vasodilatory and antihypertensive properties-offer an alternative. These effects are largely attributed to the synergistic actions of sinensetin, eupatorin, and 3'-hydroxy-5,6,7,4'- tetramethoxyflavone (TMF). The present study was designed to explore the interactions among these compounds and their collective impact on vasodilation. The current investigation utilized in vitro aortic ring assays and an orthogonal stimulus-response compatibility approach to unveil the synergistic interactions of sinensetin, eupatorin, and TMF in specific combination ratios within compatibility groups. The current results showed that G2, G7, G27, and G28 achieved vasodilatory efficacies exceeding 100%, with recorded efficacies of 190%, 148%, 117.6%, and 116.25%, respectively. Conversely, formulation F1 exhibited only additive effects with an efficacy of 88.02%. The dose-response study revealed G28 exhibited the strongest concentration-dependent vasodilatory responses, with a maximum response (RMAX) of 119.05 ± 3.29% and an EC50 of 6.78 ± 0.70 µg/mL. Conversely, G2, despite showing the highest efficacy in the orthogonal stimulus-response compatibility study, demonstrated a lower vasodilatory effect, with RMAX R and EC50 recorded at 85.78 ± 12.67% and 15.32 ± 3.07 µg/mL, respectively. These findings highlight the complexities of compound interactions in plants and underscore the potential of botanical medicines as comprehensive healthcare solutions for multifactorial diseases.
  2. Qiu Q, Zhang Z, Yang W, Tew WY, Liu C, Leong Bin Abdullah MFI, et al.
    Front Psychiatry, 2026;17:1805745.
    PMID: 42978739 DOI: 10.3389/fpsyt.2026.1805745
    INTRODUCTION: To evaluate the short-term efficacy and safety of acupuncture-antidepressant combinations for clinically diagnosed depressive disorders among participants recruited in China using a network meta-analysis.

    METHODS: PubMed, Embase, the Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to February 2025 for randomised controlled trials of acupuncture-antidepressant combinations and relevant pharmacological or acupuncture-related comparators. The principal efficacy outcome was change in Hamilton Depression Rating Scale (HAMD/HDRS) scores; safety outcomes included nausea/vomiting, dry mouth, headache, and treatment discontinuation. Risk of bias was assessed using RoB 2. Random-effects Bayesian network meta-analyses were conducted in R version 3.6.0 using gemtc version 0.8.1. Mean differences or odds ratios are presented with 95% credible intervals (CrIs), together with posterior rank-position probabilities. A standardised mean difference (SMD)-based sensitivity analysis assessed the influence of pooling HAMD-17 and HAMD-24.

    RESULTS: Seventy-seven trials (7,031 participants) were included in the systematic review. Within the principal connected eight-node efficacy network, manual acupuncture plus selective serotonin reuptake inhibitors produced the largest reduction versus SSRI monotherapy (mean difference -3.37; 95% CrI -3.86 to -2.89) and the highest probability of occupying Rank 8 (the most effective position). Electroacupuncture plus SSRIs was also associated with a greater reduction in HAMD scores than SSRIs alone (MD -2.98; 95% CrI -3.66 to -2.31). Manual acupuncture plus SNRIs also favoured combination treatment (MD -3.16; 95% CrI -6.03 to -0.28), although the interval was comparatively wide. The SMD sensitivity analysis retained benefit for both EA + SSRIs and MA + SSRIs relative to SSRIs, although their relative ordering differed from the raw-MD analysis. The available adverse-event networks did not identify statistically clear differences from SSRI monotherapy; however, sparse events and very wide CrIs limit the strength of this finding.

    CONCLUSION: Manual acupuncture plus an SSRI was associated with the largest short-term HAMD reduction in the primary raw-MD network. Relative treatment ordering differed in the SMD sensitivity analysis. The estimates should be interpreted cautiously because clinical heterogeneity, risk-of-bias concerns, sparse safety data, and limited follow-up preclude claims of equivalent safety or a preferred first-line strategy.

    SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/View/CRD420251029584, identifier CRD420251029584.

  3. Yam MF, Tew WY, Tan CS, Loh HW, Qiu Q, Yan CS, et al.
    Hypertens Res, 2025 Nov;48(11):2897-2910.
    PMID: 40968158 DOI: 10.1038/s41440-025-02298-6
    Orthosiphon stamineus Benth, commonly used in Southeast Asia for its medicinal properties, is traditionally employed to treat diabetes and hypertension. Scientific research has validated that O. stamineus extract exhibits significant vasodilatory action on rat aorta. This effect is primarily due to the synergistic interaction among key compounds: eupatorin, sinensetin and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Our previous publication identified the optimum formulation, G28, which contains eupatorin, sinensetin and TMF in the ratio of EC20:EC15:EC5. Therefore, the aim of this study was to investigate the antihypertensive effect and mechanism of action of formulation G28. In this study, aortic rings from spontaneously hypertensive rats (SHRs) and Sprague-Dawley (SD) rats were used to examine the vasodilation mechanisms. The antihypertensive effect of G28 was also assessed through repeated-dose administration in SHRs. G28 exhibited stronger vasorelaxant effects in SHR versus SD rat aortic rings, indicating higher potency under hypertensive conditions. The effect was partially endothelium-dependent, as endothelium removal reduced responses in both aortic rings. G28 retained efficacy with Nω-Nitro-1-arginine methyl ester, methylene blue and 1H-[1,2,4]Ox-adiazolol[4,3-α]quinoxaline-1-one, suggesting involvement of the NO/sGC/cGMP pathway. Additionally, G28's effect diminished with glibenclamide, barium chloride, 4-aminopyrine and tetraethylammonium, indicating potassium channel involvements. The vasorelaxant effect was not significantly altered by indomethacin, atropine, or propranolol (in SD rats only), suggesting independence from the cyclooxygenase, beta-adrenergic (in SD rats only) and muscarinic pathways. G28 also reduced intracellular Ca²⁺ in vascular smooth muscle by antagonising voltage-gated calcium channel and Inositol triphosphate receptor. In vivo, G28 significantly reduced blood pressure in SHRs over 21 days of oral administration, underscoring its potential for hypertension control. G28 shows strong antihypertensive effects via NO/sGC/cGMP, potassium and calcium channels. Its sustained blood pressure reduction in SHRs highlights potential as a promising hypertension treatment option.
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