Medicine and Pharmacology

Abstract: Medical pluralism is a global consensus, and "using each system's strengths" is common policy and clinical language. Yet advantage itself has never been decided: every claim that a system excels in a given situation remains a historical assertion—lacking a neutral metric, falsifiable conditions, and a veto mechanism. This paper names this lacuna the decidability gap of integrative medicine. Building on the author's prior multi-track cognition / system-mapping framework [4], we propose protocol-based commensuration: paradigm incommensurability at the theoretical level is left intact, while outcomes become commensurable through measurable anchors. The decision mechanism is organized into three layers: measurement (a homeostatic anchor network with a measurable-anchor specification), computation (a bidirectional cross-validation efficacy protocol and contextual routing rules), and extension (an open access protocol admitting any qualified system). Convergent validity grounds the cross-system borrowing of anchors; three safeguards—the holistic-homeostasis veto, tiered anchor admission, and evidence weighting—constrain the mechanism itself, and every anchor entering the network carries three identity markers: veto eligibility, validity grade, and evidence weight. Three standardized theoretical demonstrations and a counter-intuitive-output check show that the mechanism yields adjudications with boundary conditions, nullification clauses, and granularity beyond experiential consensus. The framework supplies an operational basis for evidence-based evaluation, multi-system coordination, and personalized medical decision-making.

Abstract: The gastrointestinal tract is increasingly recognized as an integrated regulatory system in which digestion, epithelial barrier integrity, host-microbial interactions, immune surveillance, neuroenteric coordination, and metabolic regulation are closely interconnected. Classical Ayurveda has long conceptualized gastrointestinal regulation through the interrelated principles of Agni, Ama, Grahani, Koshtha, Srotas, Dosha, and Nidana Panchaka, providing a systems-oriented framework for understanding digestive physiology and disease. However, contemporary clinical practice and translational research require objective physiological tools capable of complementing classical Ayurvedic assessment without compromising its conceptual or epistemological foundations. This review proposes an Ayurveda Biology and systems medicine framework for integrating representative gastrointestinal biomarkers into Ayurvedic diagnosis, practice, and research. Rather than treating biomarkers as direct biological equivalents of Ayurvedic concepts, the proposed framework interprets them as objective indicators of physiological domains underlying gastric function, digestive transformation, epithelial barrier integrity, host-microbial homeostasis, mucosal immunity, neuroenteric regulation, & energy homeostasis. It further illustrates how these biomarkers may complement Nidana Panchaka and Shatkriyakala, facilitating physiological characterization, clinical stratification, therapeutic monitoring, mechanistic investigation, and translational research while preserving the primacy of classical Ayurvedic reasoning. By bridging classical Ayurvedic physiology with contemporary systems biology and gastroenterology, this framework provides a scientifically rigorous yet conceptually authentic foundation for biomarker-assisted Ayurveda. The proposed Ayurveda Biology model offers a practical translational pathway for strengthening diagnosis, advancing research, fostering interdisciplinary collaboration, and restoring gut health through the convergence of holistic Ayurvedic principles and modern physiological science.

Abstract: Glucagon-like peptide-1 receptor (GLP-1R) is a focal target in antidiabetic drug discovery. Synthetic non-peptide compounds are routinely employed to investigate GLP-1R, however, scaffolds from natural products will offer us unique structural diversity to design more potent compounds. We investigated the potential of some natural compounds as agonists of GLP-1R. First, we carried out a virtual screening of 244 compounds, from 19 medicinal plants used in antidiabetic traditional medicine, against GLP-1R. We used molecular dynamics simulations, for 200ns, to further investigate the lead five compounds. Binding Free Energies (BFE), Root Mean Square Deviation (RMSD) and other parameters were employed to understand these interactions. Our results showed that lupeol (-57.23) had good BFE (kcal/mol) compared to danuglipron (-56.47), thus demonstrating more robust interactions with GLP-1R. The pocket-buried residues, CYS191 and GLN186, showed strong hydrogen bonds while the critical residue, TRP4, showed strong van der Waals interactions to stabilize the ligands. Moreover, the average RMSD (Å) of lupeol-bound GLP-1R (3.45) are comparable to danuglipron-bound GLP-1R (3.33), indicating good stability in the pocket. This potentially situates lupeol as GLP-1R agonist similar to danuglipron, and thus opens up the opportunity for more further experimental work, to validate its agonist properties on GLP1R.

Abstract: Background: Depression is a major cause of disability worldwide. Pharmaceutical antidepressants are standard treatments for moderate to severe depression; however, adverse effects, tolerability concerns, and incomplete treatment responses have increased interest in herbal alternatives. Evidence directly comparing herbal and pharmaceutical antidepressants remains inconsistent. Objective: To examine and synthesise evidence on the comparative efficacy, safety, and tolerability of herbal versus pharmaceutical antidepressants in adults with depression. Methods: A scoping review was conducted using MEDLINE, EMBASE, PsycINFO, AMED, CENTRAL, and grey literature sources. Eligible studies were primary comparative clinical studies involving adults aged 18 years and older with depressive disorders or clinically significant depressive symptoms. Data were synthesised according to Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Results: Twenty-one comparative studies met the inclusion criteria. Hypericum perforatum (St John’s wort) was the most frequently investigated herbal intervention, while selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and tricyclic antidepressants were the main pharmaceutical comparators. Standardised Hypericum perforatum preparations demonstrated efficacy comparable to selective serotonin reuptake inhibitors in mild to moderate depression. Pharmaceutical antidepressants, however, showed more consistent benefits in moderate to severe depression. Herbal interventions were generally associated with fewer adverse effects and lower treatment discontinuation rates. Conclusion: Herbal antidepressants, particularly standardised Hypericum perforatum preparations, may offer an effective and better-tolerated treatment option for some adults with mild to moderate depression. However, variations in study design, intervention standardisation, and reporting limit definitive conclusions. Further high-quality comparative research is required to strengthen the evidence base and guide clinical decision-making and support evidence-based treatment recommendations. What this study adds: This review highlights the severity-dependent efficacy and tolerability of pharmaceutical and natural antidepressants. Standardized Hypericum perforatum is identified as a potentially useful and better-tolerated treatment for mild-to-moderate depression, but it also highlights safety issues, especially herb–drug interactions, and important data gaps that need to be studied.

Abstract: Oral ulcerative and inflammatory mucosal diseases, exemplified by recurrent aphthous stomatitis (RAS) and cancer-therapy-induced oral mucositis (OM), remain challenging to treat locally because salivary clearance, enzymatic activity, mechanical movement and limited residence time constrain conventional topical drug delivery. This review examines mucoadhesive biomaterial platforms as functional delivery systems and asks whether their material properties—including retention, interfacial adhesion and controlled release—contribute therapeutic value beyond that attributable to the incorporated bioactive payload. Evidence for mucoadhesive tablets, buccal films and patches, hydrogels, polymeric nanocarriers, dissolving microneedles and electrospun systems is appraised according to an evidence hierarchy that distinguishes randomised clinical evidence from animal and in vitro findings. Mucoadhesive tablets have been associated with reductions in RAS ulcer diameter at days 5 and 7 in a small pooled analysis, while licorice-loaded dissolving and bioadhesive patches provide repeated clinical evidence for phytochemical delivery through mucoadhesive devices. Hydrogel and nanocarrier systems show preclinical benefits in wound healing and local delivery, including substantial dose sparing of triamcinolone acetonide in a microneedle platform, but remain without controlled clinical translation in the indications reviewed. Where evidence permits, retention and release are considered as material properties distinct from the biological responses they enable; however, existing studies rarely isolate the therapeutic contribution of the carrier from that of the payload. Priorities for translation include standardised mucoadhesion characterisation, physiologically relevant human oral mucosa models, botanical and phytochemical standardisation, and controlled trials comparing identical active agents in conventional versus mucoadhesive vehicles.

Abstract: Mimosa pudica L., a pantropical medicinal herb rich in polyphenols, but also containing the non-protein amino acid mimosine with known cytotoxic properties, is a case for xenobiotic pharmacology, yet its safety profile remains inadequately characterized. In this study, we quantified the major metabolite classes of an aqueous decoction of M. pudica aerial parts, evaluated its in vitro hemocompatibility in human erythrocytes, and assessed its antioxidant activity using five cell-free assays. We also employed computational tools (ADMETlab 3.0, ProTox 3.0, SwissTargetPrediction, and InflamNat) to predict ADMET properties, toxicity alerts, and potential protein targets. The decoction showed high phenolic (316.41 ± 19.58 mg GAE/g) and flavonoid (122.99 ± 12.78 mg QE/g) contents, with mimosine levels of 2.11 ± 0.13 mg/g. Antioxidant activity was concentration-dependent, with the lowest IC₅₀ in the DPPH• assay (0.23 ± 0.02 mg/mL). Hemolysis remained below 9% at all tested concentrations (0.2–1.0 mg/mL), with an HC₅₀ > 1.0 mg/mL, consistent with biocompatibility criteria for plant extracts. In silico predictions indicated that most of flavonoids and phenolic acids complied with Lipinski's rule and showed a favorable oral bioavailability, but also, significant CYP450 inhibition and alerts for genotoxicity and nephrotoxicity. Predicted molecular targets included redox-modulatory proteins such as AKR1B1, XDH, NOX4, and GSK3B. Collectively, our results demonstrate that M. pudica is a complex mixture of xenobiotics with antioxidant effects, and suggest benefits and risks associated to their individual constituents. Further in vitro and in vivo studies are needed to validate these predictions and to determine whether M. pudica can be developed into safe and effective nutraceutical or pharmaceutical preparations.

Abstract:

Atractylodes macrocephala Koidz. rhizome (Atractylodis Macrocephalae Rhizoma, AMR; Bai-Zhu) is a widely used medicinal plant, and its specialized metabolites are now being mapped onto defined molecular targets. Here we review, constituent by constituent, how AMR acts in ulcerative colitis (UC). The sesquiterpenoid lactones account for much of the activity: atractylenolide I protects the epithelial barrier (RhoA/ROCK/MLC; S100A9/AMPK/mTOR), reshapes intestinal metabolism and the microbiota (SPHK1/B4GALT2) and limits carbonic anhydrase IX-mediated ferroptosis, whereas atractylenolide II drives Nrf2-dependent antioxidant responses (in non-colitis models), and interleukin-17 receptor A is nominated as a candidate direct target of atractylenolide III—awaiting independent replication—through which it may curb macrophage M1 polarization. The polysaccharides rebalance Th17/Treg immunity and remodel the gut microbiota and its tryptophan metabolites through the pregnane X receptor, while the volatile oil and vesicle-like particles are likewise protective. We grade each mechanism by the strength of the underlying colitis-model evidence and stay explicit about what remains extrapolation. Controlled human trials are still lacking, with only very preliminary clinical observation to date. Finally, we single out endothelial-leukocyte adhesion—already exploited by anti-adhesion biologics—as the most tractable next step for translating these constituents toward the clinic.

Abstract: Bone health is a significant contributor to functional ability and well-being. Bone strength and homeostasis are maintained by a remodeling process involving bone resorption and bone formation. An imbalance of these processes increases bone turnover and triggers loss of bone structures. Excessive loss of bone mineral density and deterioration of bone microarchitecture with an augmented risk of fragility fractures are the hallmarks of osteoporosis. Osteoporosis is highly prevalent in the aging population with postmenopausal women being at particular risk. Clinical studies have reported a positive impact of polyphenol-rich nutrition on bone health. Besides phenolic compounds genuinely present in food sources, additional and potentially bioactive molecules are generated by gut microbiota from polyphenol precursors. These metabolites might contribute significantly to the health effects of dietary polyphenols. Some, such as urolithins or equol, are exclusively produced by gut bacteria and are not present in any food source (obligatory microbial metabolites). Others, such as caffeic or vanillic acid, may originate from gut microbial biotransformation of precursors or occur naturally in food sources (facultative microbial metabolites). Evidence for bioactivity of these metabolites on bone-relevant cellular pathways and metabolic bone markers is summarized stratified by study type. It seems likely that individual polyphenol-derived microbial metabolites contribute to bone-protective effects in humans. Strongest evidence is available for S-(−)-equol and consistent promising results exist for urolithin A. Notably, structurally unrelated metabolites often target the same signaling pathways. Supplementation with polyphenols appears reasonable as primary prevention for people at risk of osteoporosis or in the pre-therapeutic stage.

Abstract: Median Arcuate Ligament Syndrome (MALS) is characterised as an intra‑abdominal vascular compression syndrome in which the caudad migration of the Median Arcuate Ligament (MAL) impinges the coeliac artery and/or coeliac plexus, causing foregut ischaemia, neuropathic pain and dysautonomia. Clinically, MALS can present with postprandial epigastric pain, weight loss, nausea, vomiting, upper abdominal bloating and dysautonomia. Its common comorbidities are Postural Orthostatic Tachycardia Syndrome (POTS), Ehlers-Danlos syndrome (EDS), Mast Cell Activation Syndrome (MCAS), other abdominal vascular compression syndromes such as nutcracker and Superior Mesenteric Artery Syndrome (SMA), along with anxiety, and functional gastrointestinal disorders. Surgical decompression of the median arcuate ligament, with or without coeliac plexus intervention or endovascular stenting, can provide meaningful pain reduction and functional improvement; however, postoperative symptom recurrence, persistent dysautonomia and variable long‑term outcomes are common.This narrative review synthesises current evidence on MALS pathophysiology, symptom presentation, diagnostic imaging and management, with a particular focus on autonomic dysfunction and the emerging role of osteopathic and manual therapies. It highlights the current knowledge gap regarding autonomic pathophysiology and conservative non-surgical care in MALS, as only a limited number of case reports and series systematically assess dysautonomia or evaluate osteopathic and manual therapy. This paper aims to critically assess vascular, neurogenic, connective‑tissue, and autonomic mechanisms, evaluate current diagnostic and surgical pathways with an autonomic nervous system focus, and examine the theoretical rationale and preliminary clinical data for osteopathic and manual therapies as adjunctive or non-invasive options, thereby outlining priorities for future multimodality, phenotype‑based management and research.

Abstract: This exploratory, uncontrolled study investigated whether objective tongue mobility measurements change immediately after a brief conservative intraoral intervention, given the clinical use of the Tongue Range of Motion Ratio (TRMR) in treatment and surgical decision-making. Anonymised clinical data were analysed from 20 consecutive participants (17 females and 3 males; aged 6–84 years) receiving routine care in two private orofacial myology and temporomandibular disorder practices. Maximal mouth opening (MMO), tongue tip-to-incisive papilla (TTIP), lingual–palatal suction (LPS), and anterior and posterior TRMR were measured immediately before and after a standardised intraoral myofascial intervention lasting approximately five minutes (YTM® Introductory Protocol) and compared using paired t-tests with Wilcoxon sensitivity analyses. MMO, TTIP, and LPS increased significantly (35.5±7.0 to 40.8±6.5 mm; 26.2±7.8 to 30.4±8.5 mm; 18.8±6.6 to 22.1±8.2 mm; all p< 0.001), with large effect sizes (Cohen's dz values ranging from 0.92 to 1.45). Group-level anterior and posterior TRMR showed minimal change (both p>0.4), although a small number of participants crossed published TRMR classification thresholds. These findings indicate that absolute tongue-mobility measurements can improve immediately after brief conservative intervention, while group-level TRMR remains largely stable, raising the possibility that objective tongue mobility assessment may be influenced by immediately modifiable functional components. As this study had no control group, larger controlled trials are needed to determine whether the changes reflect intervention effects, repeated testing, or participant familiarisation.

Abstract: Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed from the amino-acid composition of epithalamin, a pineal-derived polypeptide preparation. Although historically related, the two preparations are chemically distinct and their evidence should not be considered interchangeable. This narrative review examines the mechanistic, preclinical, and human evidence for epitalon, with epithalamin studies considered separately as historical context. The strongest mechanistic evidence for epitalon involves telomerase activation and telomere elongation in human cell lines. These findings were independently replicated in 2025, with telomere extension occurring through hTERT/telomerase upregulation in normal cells and alternative lengthening of telomeres in cancer cell lines.[1] Preclinical studies have also reported age-dependent neuroendocrine effects, antioxidant-associated activity, and tissue-protective effects. In female mice, epitalon did not increase mean lifespan but increased maximum lifespan by 12.3%.[2] Human epitalon evidence remains limited to small physiological or biomarker studies and an older report in retinitis pigmentosa; no adequately powered randomized trial has established therapeutic efficacy.[1,3,4] Historical epithalamin studies have reported neuroendocrine, antioxidant, cardiovascular, and longevity-associated outcomes, but these findings cannot be directly extrapolated to epitalon. Human pharmacokinetic, dose-ranging, and dedicated prospective safety studies remain unavailable, while telomere-maintenance effects raise theoretical but unresolved questions regarding long-term oncologic safety. FDA reviewed epitalon free base and acetate through the 2026 PCAC compounding process, which does not constitute therapeutic approval. [5] Overall, epitalon demonstrates biologically relevant activity but remains clinically unproven. Independent replication, pharmaceutical characterization, pharmacokinetic and safety studies, disease-specific preclinical models, and appropriately designed human trials are needed before its role in regenerative or longevity medicine can be established.

Abstract: Ayurveda is increasingly investigated using genomics, pharmacology and systems biology, yet its global scientific landscape remains quantitatively underexplored. We conducted a bibliometric and scientometric analysis of 2,027 Scopus-indexed articles (1991–2024), identifying 7,541 authors, 762 sources and 51,735 citations. Publication growth followed a Gompertz trajectory (R² = 0.998), indicating consolidation rather than exponential expansion, with declining relative growth and increasing doubling time. Author productivity deviated from Lotka’s law, while source distribution followed Bradford’s law. Citation inequality was high (Gini = 0.728). Network analysis revealed eight thematic clusters, with antioxidant pharmacology, COVID-19-related network pharmacology and complementary medicine as major motor themes; molecular docking and network pharmacology emerged as the newest topics. India dominated output but exhibited limited international collaboration. No significant open-access citation advantage was observed. Overall, Ayurveda research is shifting toward mechanistic and translational science but remains structurally concentrated and insufficiently internationalized.

Abstract: Introduction: Plant-derived oxindole alkaloids and phytosterols, such as pteropodine (PT) and beta-sitosterol (BS), are bioactive constituents of traditional medicinal plants with recognized therapeutic potential. However, their schedule-dependent systemic immunomodulatory mechanisms and comparative safety profiles require detailed characterization. Aim of the study: To evaluate the schedule-dependent immunomodulatory, acute anti-inflammatory, antioxidant, and in vivo genotoxic safety profiles of purified beta-sitosterol and pteropodine. Materials and methods: Primary humoral immune response was assessed in BALB/c mice by IgM plaque-forming cell (PFC) assay under three administration schedules (24 h prior, simultaneous, and 24 h post-SRBC immunization). Acute anti-inflammatory activity was evaluated using TPA-induced mouse ear edema. In vitro antioxidant capability was tested via DPPH radical scavenging. In vivo genotoxicity was determined by the micronucleus assay in polychromatic erythrocytes over 96 h. Comparative cytotoxic screening on Chang liver and HepG2 cells was performed by cell adhesion evaluation. Results: Both compounds demonstrated a schedule-dependent immunomodulatory profile: pre-treatment or simultaneous administration with antigen significantly enhanced IgM-PFC counts, whereas post-immunization administration exerted dose-dependent regulatory suppression. BS and PT significantly inhibited TPA-induced ear edema in a dose-dependent manner (66.0%–84.3% and 67.5%–71.1%, respectively), comparable to indomethacin (70.6%). Both compounds showed concentration-dependent DPPH scavenging activity. Neither compound increased micronucleated erythrocytes in vivo, demonstrating genotoxic safety. Conclusions: Beta-sitosterol and pteropodine act as biocompatible, multi-target natural modulators with significant anti-inflammatory and schedule-dependent immunomodulatory activities, providing a solid scientific basis for their pharmacological application.

Abstract: Background: A person with depression, unresolved trauma, a substance problem, and cognitive complaints is treated differently depending on which practitioner they consult. A psychiatrist draws on the monoaminergic and glutamatergic literature. A licensed facilitator draws on the session literature. A naturopath draws on the botanical and nutritional literature. Each draws on a defensible evidence base, and none of the three literatures routinely cites the other two. No single reference covers the agents acting on these conditions across the disciplines that use them, with the evidentiary standing of each claim visible and the boundary of each practitioner’s authority stated. Objective: To organize that agent population by mechanism of action rather than by regulatory status or professional tradition, assign an explicit evidence tier to every claim, characterize the route and bioavailability for every agent, and derive an operational logic for safety gating, interaction adjudication, and protocol construction that practitioners from differing disciplines and with varying prescribing authority can apply within their own scope. Methods: A structured review was conducted with framework development, defining fifteen mechanism classes based on receptor pharmacology and downstream signalling. Each agent was characterized by its mechanism, dose range, route, established bioavailability, onset, duration, evidence tier, contraindications, and potential interactions. The evidence was evaluated through an international literature review and categorized into a single standardized tier system, regardless of jurisdiction: T1 for randomized controlled trials, T2 for controlled studies with limitations, T3 for observational or open-label studies, T4 for mechanistic evidence only, and T5 for traditional use. Results: Fifteen classes are outlined across 154 subsections, covering areas like glutamatergic modulation, serotonergic psychedelics, entactogens, non-5-HT2A psychoactives, monoaminergic and inhibitory modulation, neurotrophic and neuroimmune agents, adaptogenic and mitochondrial support, pharmacokinetic modification, potentiation, cholinergic modulation, and circadian phase. Seventy-six agents are individually characterized. A condition matrix links them to sixty-eight indications, including cluster headache, tic disorders, traumatic brain injury, chronic pain, burnout, and insomnia, which are often missing from reviews despite substantial supporting data. The safety measures include six safety gates, eighteen interaction rules with specified severity, a seven-step construction process, and a role-scope matrix. Route and bioavailability are detailed for each agent: five deliver about the administered dose; several widely used agents reach systemic circulation at one to ten percent; and four are pharmacologically inert via their primary route. Conclusions: A mechanism-first organization enables the evaluation of agents with varying evidentiary credibility and regulatory statuses within a single framework, without undervaluing weaker evidence or overestimating stronger cases. Three key points follow. The evidence tier pertains to the agent-indication-dose triplet, not the agent itself: for example, piracetam shows T1 evidence for myoclonus at 24 g daily and T4 for cognition at any dose. An additional axis, circadian phase, runs alongside dose, mechanism, and route; a shifted rhythm indicates deficiency and calls for the opposite intervention. When absorption or first-pass metabolism limits a compound rather than receptor pharmacology, the issue is a formulation problem and should be labelled as such. This framework is designed for complementary and adjunctive practices, highlights sections needing prescribing authority, and does not replace personalized clinical judgment.

Abstract: Acupuncture is supported by a long clinical tradition and a growing body of mechanistic research, yet the classical meridian system remains difficult to reconcile with conventional anatomical models. The persistent difficulty may arise from a category error: meridians have often been sought as discrete anatomical tubes, whereas the relevant biological object may be a dynamic control and information system. Here we propose the Meridian-Program Hypothesis, which reinterprets the acupuncture system as a five-layer bioelectrical and mechanochemical control network. In this framework, connective-tissue and neural substrates form the hardware layer; local bioelectrical, mechanical, chemical and optical signals form the code layer; central nervous system processing acts as a compiler that assigns context-dependent physiological meaning; neuroimmune, endocrine and molecular pathways constitute the execution layer; and acupuncture functions as a parameterized state-correction input that may shift dysregulated states toward homeostasis. The model does not claim that traditional meridians are already proven anatomical structures. Instead, it offers a testable systems-level language that integrates evidence from electrical impedance studies, fascia research, somatotopic electroacupuncture circuits, neuroimaging, neuroimmune modulation and molecular network studies. We outline three experimental routes: multimodal signal fingerprinting of acupoints, causal chain testing from peripheral input to central processing and organ response, and mapping of pathology-specific stimulation parameters. By turning the meridian question from 'Where is the structure?' to 'How does the control system operate?', the hypothesis may help bridge traditional acupuncture theory with contemporary neuroscience, systems biology and precision neuromodulation.

Abstract: Background/Objectives: The aim of this review is to present the current possibilities for using low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) in musculoskeletal rehabilitation programs for knee osteoarthritis (KOA). Methods: A narrative review of the scientific literature published in the following databases was conducted: PubMed, ScienceDirect, Google Scholar, and ResearchGate. Scientific articles containing information regarding the application and efficacy of laser therapy (LLLT and/or HILT) for musculoskeletal rehabilitation in KOA were searched for. This review included observational studies, randomized controlled trials, systematic reviews, and meta-analyses published from January 2000 to June 2026. Results: Data were found indicating a high degree of disability due to degenerative musculoskeletal conditions. This requires the optimization of osteoarthritis management strategies. Evidence of varying levels of significance was identified regarding the benefits of LLLT and/or HILT in reducing osteoarthritis symptoms. However, at this stage, no firm recommendations have been made regarding the inclusion of LLLT and/or HILT in musculoskeletal rehabilitation programs. Conclusions: The use of LLLT and/or HILT therapeutic lasers in musculoskeletal rehabilitation programs may have a positive effect on osteoarthritis by improving tissue trophism and pain reduction, as well as improving range of motion and functional activity, and may also help to reduce the use of pharmacological agents. However, there is no conclusive evidence, and no strong recommendations were found for the inclusion of LLLT and/or HILT in osteoarthritis management programs. This necessitates future high-quality scientific studies with standardized protocols for laser therapy.

Abstract: Objectives: The study determined antibiotic resistance profiles of surgical wound’ multidrug-resistant (MDR) isolates belonging to the ESKAPE group and evaluated antibacterial and antibiofilm activities of geraniol (G), carvacrol (C), and eugenol (E), individually and in the selected binary mixtures against them. The cytotoxicity of monoterpenes and their combinations was also assessed. Methods: The antibacterial activity against E. faecium, S. aureus MRSA, K. pneumoniae, A. baumannii, P. aeruginosa and Enterobacter spp. was assessed in microdilution assay. Antibiofilm activity was tested in crystal violet assay. Cytotoxicity of the tested monoterpenes was estimated in XTT assay. Results: C proved the strongest antimicrobial activity (MIC 0.32±0.24 mg mL-1). Antibacterial checkerboard assay, used to study interactions, showed synergism between all monoterpenes. Significant biofilm inhibition (in crystal violet assay) was found for sole monoterpenes, with the most pronounced inhibition for G (38.78–84.72%, p< 0.05). The most significant biofilm eradication was demonstrated for C (25.21-61.34%, p< 0.05), while the G (28.83-55.26%) and E (21.74-52.83%) exhibited a weaker effect. G-C mixtures were further studied for the antibiofilm effect, showing notable inhibition of biofilm formation on all isolates except P. aeruginosa. However, the G-C mixtures exhibited biofilm eradication activity solely against P. aeruginosa. Cytotoxicity tested on normal human MRC-5 fibroblasts showed no cytotoxicity at tested doses of G, E and C, while G-C mixtures were less cytotoxic than povidone-iodine (p< 0.05), used as control. Conclusions: All monoterpenes and G-C mixture proved significant antibacterial and antibiofilm potential against ESKAPE isolates, and acceptable impact on cell viability.

Abstract: Cold hypersensitivity in hands and feet (CHHF) affects 20–52% of East Asian populations, is more prevalent in women, and is managed with vasodilators in Western medicine or herbal therapies in traditional East Asian medicine. This study was conducted to compare the pharmacological characteristics of two heat-clearing (HCHs, Scutellariae Radix and Coptidis Rhizoma) and two blood-tonifying herbs (BTHs, Angelicae Sinensis Radix and Paeoniae Radix Alba) used for CHHF. Candidate herbs were selected based on herbology classifications, PubMed searches, and the Korean Medicine Clinical Practice Guideline for CHHF. A total of 61 active compounds and 323 corresponding protein targets with CHHF were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), standardized via UniProt, and intersected with CHHF-related genes from GeneCards. Protein–protein interaction networks were con-structed, core targets identified, and functional enrichment analyses performed using Gene Ontology and Reactome databases. A total of 166 herb–CHHF common targets were identified, including 24 shared across all four herbs. HCHs were primarily enriched in hemostasis-, immune-, and signaling-related pathways, whereas BTHs were associated with immune regulation, metabolism, and neuronal modulation. Notably, Scutellariae Radix and Paeoniae Radix Alba showed substantial overlap in enriched pathways. These findings suggest that HCHs and BTHs may act through distinct yet complementary mechanisms in CHHF, providing a mechanistic basis for combined traditional use.

Abstract: Background: Malignant melanoma is characterized by molecular heterogeneity, adap-tive signaling, and limited durability of therapeutic responses. This exploratory study examined a chemically characterized dual-oil formulation composed of cold-pressed Prunus dulcis oil and Pinus sylvestris needle essential oil as an integrated life-science model linking formulation chemistry, comparator-context molecular docking, and cel-lular viability. Methods: GC-MS/FAME profiling defined the principal formula-tion-associated markers. Docking was used to prioritize structurally plausible interac-tions across a melanoma-relevant target panel, while Neutral Red Uptake assays quan-tified 24-h viability in B16F10 melanoma cells and MRC-5 fibroblasts. Spearman rank analysis was applied to the concentration–viability series to test monotonic biological coherence; a direct component-level docking-to-cellular correlation was prospectively evaluated for estimability. Results: The combined formulation yielded estimated IC50 values of 1.42% in B16F10 cells and 4.85% in MRC-5 cells (selectivity index, 3.41). Across the complete concentration range, the relationship was non-monotonic (B16F10: ρs = −0.429, p = 0.289; MRC-5: ρs = −0.381, p = 0.352), whereas the descending high-dose branch (≥0.37% v/v) showed strong inverse rank associations (B16F10: ρs = −1.000, p < 0.001; MRC-5: ρs = −0.900, p = 0.037). A statistically valid direct in silico–in vitro Spear-man coefficient could not be calculated because compound-resolved cellular pheno-types were unavailable for the six docked chemical markers. Conclusions: The data support a biologically coherent, concentration-dependent cytotoxic phenotype within the descending exposure range and define a rigorous framework for future com-pound-matched computational–experimental validation. The study should be inter-preted as hypothesis-generating rather than as evidence of cellular target engagement or therapeutic efficacy.

Abstract:

The corm of Colocasia esculenta (L.) Scott is widely used for food and treating gastric problems. However, its gastroprotective activity remains unexplored. This article aims to investigate the gastroprotective activity of the ethanol extract of C. esculenta corm (EECE) in ethanol-induced gastric ulcer in rats. EECE was analyzed for nutritional composition (proximate and vitamin C) and phytochemical composition (total phenol content, total flavonoid content, and quercetin levels), followed by metabolite profiling and an in vivo study. Male Wistar rats were randomly assigned to seven groups: (1) normal control, (2) negative control, (3) sucralfate group, (4) quercetin group, and three EECE groups at doses of (5) 200 mg/kg BW, (6) 400 mg/kg BW, and (7) 800 mg/kg BW. Following a two-week treatment period, all groups except the normal group were exposed to 70% ethanol. Post-mortem analysis included macroscopic and histopathological examination of gastric tissue, as well as Western blot analysis to investigate NF-κB p65 expression. EECE contains high moisture, ash, fat, and protein, and low carbohydrate levels, vitamin C at 417.73 mg/100 g, total phenol content of 833.43 mg GAE/100 g, total flavonoid content of 1,178.82 mg QE/100 g, and quercetin at 261.76 mg/100 g. UHPLC–HRMS/MS analysis revealed amino sugars, conjugated amino acids, lipids, phenolics, and minor cyanogenic glycosides. EECE significantly reduced ulcer area percentage in an ethanol-induced gastric ulcer model (p < 0.05). It increased mucosal thickness, reduced polymorphonuclear cell infiltration, and decreased NF-κB p65 expression. The gastroprotective effects of EECE are mediated by enhancing gastric mucosal defense and inhibiting NF-κB p65 expression, thus highlighting its potential as a promising gastroprotective adjunct therapeutic agent.