Background: Incorporating sex as a biological variable (SBV) is recognized as essential for improving the reliability, reproducibility, and generalizability of pharmacological research. This principle is codified in international policies and guidelines, yet implementation remains uneven, especially in phytomedicine. Phytomedicines are a major component of healthcare worldwide, with 65% of the global population relying on them in both regulated and traditional contexts. Globally, phytomedicines are used by males, females, intersex and non-cis gender persons, all of whom may present specific safety and efficacy considerations and warrant full inclusion in pre-clinical to clinical research pipelines. However, in contemporary settings, phytomedicine lags in SBV best practices relative to Western allopathic standards for research design. Methods: We conducted a non-systematic review and in silico data mining to quantify sex/gender representation in recent preclinical and clinical phytomedicine studies, complemented by targeted case studies of sexually dimorphic safety/efficacy. We also summarize the historical role of women and gender-diverse people as users and providers within Traditional and Integrative Medical Systems (TIMSs). Results: Across rodent and human studies, females are under-represented relative to males, and sex is rarely reported for cell lines. Intentional inclusion of intersex and other gender-diverse populations is largely absent. Case studies illustrate plausible sex-associated differences in pharmacokinetics, pharmacodynamics, and adverse event profiles. TIMSs historically address women's health needs and include substantial participation by female practitioners; however, contemporary SBV practices remain less standardized than in Western allopathic pipelines. Conclusions: SBV integration in phytomedicine is needed to strengthen safety, efficacy, and regulatory-grade evidence. Practical barriers include legacy datasets without sex metadata, limited intersex animal models, and uneven resources across settings. We outline feasible, stepwise practices to improve SBV adoption in a manner compatible with TIMS contexts and recommend expanding current guidelines to better support diverse research environments while maintaining scientific rigor.

Cadmium (Cd) is an environmental toxicant originating from both natural processes and human activities. Cd has been strongly associated with multiple diseases, including breast cancer (BC). Background/Objective: Environmental Cd exposure represents a significant contributor to BC onset and progression. Cd-induced breast carcinogenesis is driven by a constellation of molecular events, including DNA damage, oxidative stress (OS), and the dysregulation of key signaling pathways. These include the ERK/JNK/p38 MAPK cascade, the PI3K/AKT/mTOR axis, NF κB activation, and Wnt signaling, all of which collectively promote tumor initiation, survival, and metastasis. This review underscores the complex interplay between Cd exposure and its effects on cancer-triggering factors. Methods: The complexity of the mechanisms Cd-induced BC, underlying Cd-induced BC makes it challenging to treat, highlighting the need for novel therapeutic strategies that complement or enhance conventional chemotherapy. Therefore, this review was developed by reviewing the literature and presenting the different aspects of the challenge associated with Cd exposure and BC therapy. Results: Phytochemicals, especially phenolics, alkaloids, carotenoids, terpenoids, and related plant-derived compounds, have emerged as promising candidates for mitigating Cd-induced BC. Their antioxidants, anti-estrogenic, and anti-inflammatory properties position them as potential chemopreventive and therapeutic agents capable of counteracting Cd's molecular toxicity. Conclusions: The review presents current evidence linking Cd exposure to BC development and highlights the protective potential of selected phytochemicals in preventing or attenuating Cd-induced BC. Understanding these interactions reinforces the importance of phytochemical-based interventions as a strategy to reduce Cd-related cancer risk and support breast health.

Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug delivery systems. Therefore, encapsulation of natural products in a carrier addresses the above concern. Drug delivery systems, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are promising carriers for effective release, consisting of solid and liquid lipids, which enhance efficiency, stability, and controlled release, thereby minimising bioavailability limitations. This review consolidates current studies on the formulation methodologies, mechanisms of action, and therapeutic applications of NLCs, emphasizing their use in the treatment of conditions such as cancer, neurological disorders, and cardiovascular diseases. The results demonstrate that NLCs substantially enhance the bioavailability and therapeutic efficacy of antioxidants, thereby improving their targeted administration and clinical effects. Nonetheless, difficulties in clinical translation remain, including drug loading capacity, regulatory authorisation, and the need for pervasive research on cytotoxicity. This article highlights important areas for future inquiry, specifically the optimisation of NLC formulations, the enhancement of targeting accuracy, and the resolution of safety issues to enhance their clinical application.

Background/Objectives: Burn injuries present significant treatment challenges due to the intricate nature of the healing process. Bombyx mori L. (silkworm) derivatives, containing healing-promoting proteins such as sericin and fibroin, as well as the anti-inflammatory enzyme serrapeptase, have shown promise as potential healing agents. This study aimed to identify the optimal dosage of silkworm body and gland extracts for burn healing, compare the selected dose's effectiveness with that of silkworm cocoons, and assess the combined healing effects of a cocoon dressing and a silkworm body extract gel. Methods: An experimental model was employed using hairless SKH-hr2 female mice subjected to standardized second-degree burns. The mice received treatments with various formulations of silkworm body and gland extracts, silkworm cocoons, and a combined application of a cocoon dressing and silkworm body extract gel. Results: The most effective treatments were the cocoon dressing and the combination of cocoon dressing with 60% body extract gel. By Day 20, complete healing (100%) was observed in the 20% and 60% body and gland extract groups, while the cocoon and 60% gland extract groups exhibited 60% healing, significantly higher than the control group (0% healing). Wound contraction analysis showed the greatest reduction in surface area from Day 3 to Day 17 in the cocoon and 60% body extract groups (p < 0.05). Histopathological assessments revealed that the combination group exhibited the least tissue damage (score: 7), compared to the control (score: 10-13). Conclusions: The study highlights the poorly examined therapeutic potential of silkworm body and gland extracts, demonstrating their efficacy in accelerating burn healing. The effects observed by the silkworm cocoon and body extract suggests a novel and promising approach for burn wound management, warranting further clinical exploration.

Osteoarthritis (OA) is the most common joint disorder, with a social and financial burden that is expected to increase in the coming years. Currently, there are no effective medications to treat it. Due to limited treatment options, patients often resort to supplements, such as collagen hydrolysates (CHs). CHs are products with low molecular weight (MW) peptides, often between 3 and 6 kDa, and are a result of industrialized processed collagen. Collagen extraction is often a by-product of the meat industry, with the main source for collagen-based products being bovine, although it can also be obtained from porcine and piscine sources. CHs have demonstrated positive results in clinical trials related to joint health, such as decreased joint pain, increased mobility, and structural joint improvements. The bioactivity of CHs is primarily attributed to their bioactive peptide (BAP) content. However, there are significant knowledge gaps regarding the digestion, bioavailability, and bioactivity of CH-derived BAPs, and how different CH products compare in that regard. The present review discusses CHs and their BAP content as potential treatments for OA.

Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ[2] = 8.55, p = 0.033) and type of surgery (χ[2] = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.

Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca2+ chelation. EECS also depolarized the β-cell membrane and elevated intracellular Ca2+, suggesting the involvement of a KATP-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.

Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. What are the factors that are currently contributing to this new possible epidemiological dynamic? Could these be of a structural nature? Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections.

This study provides epidemiologic and clinical characteristics of 492 consecutive patients diagnosed with SARS-CoV-2 infection at King Faisal Specialist Hospital and Research Centre in Saudi Arabia between March and September 2020. Data were collected from electronic case reports. The cohort was 54% male, with 20.4% aged >60 years, 19.9% aged 31−40 years, and 17% aged 41−50 years. The median incubation period was 16 days, with upper and lower 95% quartiles of 27 and 10 days, respectively. Most patients (79.2%) were symptomatic. Variables significantly different between symptomatic and asymptomatic patients were age, blood oxygen saturation percentage, hemoglobin level, lymphocyte count, neutrophil to lymphocyte (NTL) ratio, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. Asymptomatic patients were mostly younger, with lower body mass index and ALT and AST levels but higher lymphocyte counts, NTL ratio, and CD4, CD8, natural killer cell, IgG, and IgM levels. Factors associated with increased risk of mortality were age (>42 years) and comorbidities, particularly diabetes mellitus and hypertension. Patients who were not given an antiviral regimen were associated with better prognosis than patients who received an antiviral regimen (HR, 0.07; 95% CI, 0.011−0.25). These findings will help clinicians and policymakers adopt best management and treatment options for SARS-CoV-2 infection.

Background: Some ergogenic medicinal plants are used in exercise and sport in Africa in order to increase sport performance. However, data on their composition and their possible impacts on health are limited. This study was initiated to provide ethnobotanical data on plants traditionally used to optimize physical performance and to perform a qualitative characterization of their main chemical groups. Methods: Ethnobotanical surveys in two communes (Dedougou and Nouna), of the region of Boucle du Mouhoun, Burkina Faso and phytochemical analyses of the most interesting plants were conducted. Results: A total of 50 respondents including traditional hunters dozo, farmers, healers, herbalists, marabouts, etc., were interviewed. Fifty-two species used in the optimization of exercise and sports have been identified. The most cited species were Cassia sieberiana, Tamarindus indica, Annona senegalensis, Gardenia sokotensis, Securidaca longepedunculata, and Ficus tonningii. These plants are known to prevent muscle and skeletal disorders, aches and pains, and mental disorders. The study identified several types of plants including those displaying stimulation, anxiolytic, sedative, adaptogenic, or erythropoietic activities. Phytochemical screening revealed the presence of phenolic compounds, alkaloids, terpenes, and steroids, which are similar molecules families of those of doping molecules. Additionally, TLC screening allowed the characterization of numerous terpene and flavonoid compounds including rutin. Conclusions: The possible structural similarity of the characterized chemical groups of these species with those of doping families raise concerns about the consequences of their consumption. However, the identification of the active molecules of these species remains to be performed in order to predict the real risks associated with their consumption.

Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using 1H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P 2 and Q 3.

Background: Tamoxifen (TMX) has proven to be effective in the prevention and treatment of breast cancer. However, long-term use of TMX is associated with hepatic steatosis, oxidative liver injury and hepatocarcinoma. Buchholzia coriacea seeds (BCS) have been widely applied in traditional medicine due to their nutritional and therapeutic potentials. This study investigates the protective effect of hydroethanolic extract of (defatted) B. coriacea seeds (HEBCS) against TMX-induced hepatotoxicity in rats. Methods: Thirty-six (36) male albino rats were divided into six groups (n = 6/group). Group I served as control. Group II received 50 mg/kg/day TMX orally (p.o.) (TMX) for 21 days, group III received TMX plus 125 mg/kg/d HEBCS p.o. (HEBCS 125) for 21 days, group IV received TMX plus 250 mg/kg/d HEBCS p.o. (HEBCS 250) for 21 days and rats in group V and VI received HEBCS 125 and HEBCS 250 respectively for 21 days. Results: Compared with the control, TMX caused a significant increase (p < 0.05) in serum hepatic function biomarkers: alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase by 57%, 60% and 68% respectively. TMX also caused a significant increase in hepatic triglycerides level by 166% when compared with control and a significant decrease in serum HDL-cholesterol level by 37%. Compared with control, hepatic marker of inflammation, tumour necrosis factor alpha (TNF-α) increased significantly by 220%, coupled with significant increase in expression of interleukin 6 and cyclooxygenase 2. There was also significant increase in levels of Biomarkers of oxidative stress, nitric oxide, malondialdehyde and protein carbonyls in the TMX group by 89%, 175% and 114% respectively when compared with the control. Hepatic antioxidants, reduced glutathione (GSH) level and activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) decreased significantly in the TMX group by 35%, 67%, 41%, 59% and 53% respectively when compared with the control. However, HEBCS at 250 mg/kg significantly protected against TMX-induced hepatotoxicity by decreasing hepatic triglyceride content, serum hepatic function biomarkers, hepatic inflammation and oxidative stress with significant improvement in hepatic antioxidant system. Histopathological findings show that HEBCS alleviate TMX-induced hepatocyte ballooning. Conclusions: Current data suggest that HEBCS protected against TMX-induced hepatotoxicity in rats. HEBCS may be useful in managing TMX-induced toxicities in breast cancer patients. It may also be helpful against other forms of liver injury involving steatosis, inflammation, free radicals, and oxidative damage.

Cancer is a global health and economic issue. The majority of anticancer therapies become ineffective due to frequent genomic turnover and chemoresistance. Furthermore, chemotherapy and radiation are non-specific, killing all rapidly dividing cells including healthy cells. In this review, we examine the ability of some natural products to induce lysosomal-mediated cell death in neoplastic cells as a way to kill them more specifically than conventional therapies. This list is by no means exhaustive. We postulate mechanisms to explain lysosomal membrane permeabilization and its role in triggering cell death in cancer cells.

Background: Very few studies of the antiviral potential of lignosulfonates have been published. With the aim of oral application, among various groups of natural products, the relative antiviral potency of lignosulfonate and its ability to rapidly inactivate viruses were investigated. Methods: As target cells, MT-4 cells in suspension and attached Vero cells were used for infections with human immunodeficiency virus (HIV) and human herpes simplex type-1 virus (HSV). Mock- or virus-infected cells were incubated for 3-5 days with various concentrations of test samples, and the viable cell number was determined with the MTT method. For the shorter exposure experiments, higher titers of HIV or HSV were exposed to test samples for 10 or 3 min, diluted to a normal multiplicity of infection (MOI), and applied to the cells. Antiviral activity was quantified by using the chemotherapy index. Results: In the long-exposure system, lignosulfonates showed comparable anti-HIV activity with those of AZT, ddC, and sulfated polysaccharides, and it exceeded those of hundreds of tannins and flavonoids. When the exposure time was shortened, the chemotherapeutic index of the lignosulfonates for HIV was increased 27-fold. At a physiological pH, lignosulfonate showed higher anti-HIV activity than commercial alkali-lignin, dealkali-lignin, and humic acid, possibly due to the higher solubility and purity. Conclusions: With their rapid virus-inactivation capabilities, lignosulfonates may be useful for the prevention or treatment of virally induced oral diseases.