Abstract: Objectives: This study aims to investigate the analgesic potential of extracts from 3 Capsicum species, namely Capsicum chinense (CC), Capsicum frutescens (CF), and Capsicum annuum (CA), using a hot plate test in mice. In addition, the study identified the key bioactive compounds in the extracts through a combined analysis of Fourier Transform Infrared Spectroscopy (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and molecular docking studies. Materials and Methods: During the experimental procedures, extracts from the fruit, stem, and leaves of 3 Capsicum species were prepared using methanol, hexane, and distilled water (aquadest) as solvents. The chemical composition of these extracts was profiled and classified through Fourier-transform infrared (FTIR) spectroscopy combined with cluster analysis. Subsequently, the analgesic activity of the samples was assessed in vivo using the hot plate test in mice. Gas chromatography-mass spectrometry (GC-MS) was used to identify the bioactive compounds present in both the most potent and least potent extracts. Molecular docking studies were then conducted to predict the interactions between these compounds and specific analgesic protein targets, namely 5IKQ, 4TLM, and 4EJ4. Results: The results showed that the aquadest fruit extract of CC had the highest analgesic activity, while extracts from CF and CA had minimal effects. GC-MS analysis showed that the extract with minimal effects contained terpenoids, sterols, vitamins, hydrocarbons, and fatty acids. However, CC was rich in alkaloids capsaicin (4.38%) and dihydrocapsaicin, O-acetyl- (2.26%), terpenoids (nerolidyl acetate) (11.32%), phenolics (2-methoxy-phenol) (1.37%), and fatty acid derivatives. Molecular docking studies confirmed that capsaicin and dihydrocapsaicin, O-acetyl- exhibited strong binding affinities with analgesic protein targets 5IKQ (-8.0 kcal/mol), 4TLM (-5.3 and -4.9 kcal/mol), and 4EJ4 (-7.3 and -6.5 kcal/mol) outperforming the reference drug sodium diclofenac (-8.3, -5.9, and -6.6 kcal/mol). Conclusion: This study described the significant analgesic potential of CC extracts, particularly the aquadest fruit extract, as a promising candidate for developing new pain management therapies.

Abstract: Zingerone (ZiN), a polyphenolic alkanone derived from ginger (Zingiber officinale), is a natural bioactive compound with a broad spectrum of pharmacological properties. This review explores its multifaceted therapeutic applications, including antivirulence, antioxidative, anti-inflammatory, anticancer, and various other biological properties, as well as its potential application in diverse avenues. Apart from collating most-recent scientific literature on the therapeutic role, we provide an extensive overview of ZiN's safety, toxicity, bioavailability, and its potential as a promising candidate for drug development. Further, we shed light on the recent advancements made towards formulating different drug delivery systems, including nanoparticles and liposomal formulations, that have significantly improved the therapeutic efficacy and pharmacokinetics of ZiN. Moreover, we present findings from preclinical studies (in vitro and in vivo), that establish and validate its protective efficacy against human disorders/diseases like diabetes, chronic inflammation, acute diarrhoea, malignant cancers, radiation- and chemical-induced oxidative stress, and bacterial infections. The intellectual property and patents related to ZiN formulations and its therapeutic utility have also been documented. Besides clinical trials on ZiN and its derivatives are in their infancy and presently underway for validating its safety and effectiveness for biomedical applications. Overall, this review presents an updated insight into the biological attributes and pharmacological prospects of ZiN, comprehensively establishing its multifarious nature as a potent drug.

Abstract: Background: Anxiety disorders have a 7.3% worldwide prevalence and, considering the long period of treatment, developing new efficient and safer pharmacological tools is critical. Essential oils consist of highly concentrated lipophilic compounds from plants with therapeutic potential effects—Lavandula burnatii, produced in Córdoba with high levels of active pharmaceutical ingredients. The evidence indicates that lavender essential oil could induce anxiolytic effects, however, more systematic studies are needed. Methods: To test the anxiolytic attributes of Lavandula burnatii, male Wistar rats (200-260g) were injected intraperitoneally with 2 different doses of essential oil (30 /80 mg/Kg) or vehicle (Myritol 318, a high-purity vegetable oil), once (acute) or for 7 days. One hour after the last administration, the anxiolytic effects were evaluated using the following behavioral tests: dark-light box and elevated plus maze. The open-field test was used to assess locomotor activity. Results: Our results showed that the lower dose of lavender essential oil induces anxiolytic effects since it increases the time spent in the aversive compartment in each evaluation. The acute administration has no impact on the behaviors evaluated. The higher dose is comparable with the control group and does not show significant differences. Conclusion: More studies are needed to better characterize the beneficial effects of this essential oil for anxiety disorders and to establish an adequate dosage range.

Abstract: Background/Objectives: Our group has been trying to bring scientific rationale to the quality, safety and efficacy of Brazilian medicinal plants. This work was the first step of a broader project evaluating the potential of Monteverdia ilicifolia capsules for managing dyspepsia in a randomized, double-blind clinical trial. M. ilicifolia is a native species widely used in Brazilian traditional medicine for treating gastric disturbances. The central aim of the present work was to develop capsules containing an M. ilicifolia standardized spray-dried extract (SDP) on a lab scale and to transfer the process to a Brazilian pharmaceutical industry for a scale-up approach, achieving high-quality capsule production for our clinical trial Methods: Quality control of raw materials and derivative products followed the official plant monograph, specifically total tannin content (Folin-Dennis method) and epicatechin content (HPLC analysis). The leaves of M. ilicifolia were used to prepare an infusion for 15 minutes. The infusion was filtered and concentrated, and cornstarch and colloidal silicon dioxide were added to produce a M. illicifolia spray-dried powder, which was subsequently encapsulated. Results: The raw material and SDP had high total tannins and epicatechin content. The number of capsules required to achieve 860 mg of SDP was three capsules size 0. Due to the blind tests, the dose of 400 mg and the omeprazole (20 mg) were also encapsulated in three capsules size 0. The capsules prepared on a semi-industrial scale showed an immediate release profile. The outcomes from this study evidenced that the developed technology produced suitable spray-dried powder to be employed as hard gelatin capsules for clinical trials. Conclusions: Although a traditional aqueous extract was the starting point of the work, the technological development of SDP was successfully achieved and transferred to the Brazilian pharmaceutical industry. Following Good Manufacturing Practices, this approach can provide efficient (and quickly) high-quality SDP and corresponding capsules for clinical evidence-based phytotherapy.

Abstract: (1) Cleft palate is a common birth defect worldwide and is caused by both genetic and environmental factors. Intrauterine drug exposure is one of the environmental factors that can induce cleft palate. Mycophenolate mofetil (MPM) is an immunosuppressant drug with teratogenic effects, including cleft palate. However, the research on MPM-induced cleft palate remains limited. Sasa veitchii extract (SE), a medical plant extract, is commercially available in Asia and has been reported to show the effectiveness on oral diseases. The purpose of the present study is to evaluate whether SE protects against MPM-induced immunosuppression in human embryonic palatal mesenchymal (HEPM) cells. (2) Methods: Cell viability and G1 phase-related cell cycle markers were assessed by cotreatment with MPM and SE. Furthermore, we quantified cleft palate-associated miRNA levels and the expression of its downstream genes. (3) Results: MPM treatment reduced cell viability in a concentration-dependent manner. Co-treatment with SE alleviated MPM-induced inhibition of HEPM cell proliferation. Additionally, SE reduced MPM-induced miR-4680-3p upregulation and the downregulation of its downstream genes (ERBB2 and JADE1). (4) Conclusions: These results suggest that SE alleviated MPM-induced cell proliferation inhibition through modulating miR-4680-3p expression.

Abstract: The increasing prevalence of multi-drug-resistant bacteria presents a significant challenge to traditional antibiotic therapies, emphasizing the urgent need to explore alternative antimicrobial sources. Bioactive secondary metabolites derived from plants have long been recognized for their therapeutic potential in traditional medicine and serve as vital raw materials for modern pharmaceuticals. This study investigates the antimicrobial properties of Loropetalum chinense var. rubrum, a species traditionally used in Chinese folk medicine. Qualitative phytochemical analyses of crude leaf extracts revealed the presence of several bioactive compounds, including carbohydrates, glycosides, proteins, amino acids, flavonoids, phenols, and tannins. The antimicrobial activity of these extracts was assessed using disc diffusion assays, demonstrating significant growth inhibition against both gram-positive and gram-negative pathogenic bacterial strains, including Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Enterobacter aerogenes, and Escherichia coli. Inhibition was concentration-dependent, with activity observed at extract concentrations ranging from 62.5 µg/disc to 500 µg/disc. This study underscores the promising antimicrobial potential of Loropetalum chinense var. rubrum, highlighting its potential as a valuable source for developing new antimicrobial agents to combat resistant infections.

Abstract: Background/Objectives: The adaptogenic effects of Ashwagandha root extract are evident. An earlier study showed the therapeutic effects of a once-daily sustained-release (SR) formulation (300 mg) of Ashwagandha root extract over an extended period. This study aimed to evaluate the efficacy and safety of Ashwagandha root extract SR (AshwaSR) 150 mg and 300 mg capsules in reducing stress in healthy adult, stressed subjects. Methods: In this double-blind, randomized, placebo-controlled trial, healthy subjects with Perceived Stress Scale (PSS) score 14-26 were randomized (1:1:1) to AshwaSR 150 mg (group A) or 300 mg (group B) or placebo (group C). Change from baseline to day 60 was evaluated for stress levels, sleep quality, happiness level, eating behavior, and serum cortisol levels in all groups. Results: Of 135 subjects randomized, 126 completed the trial (mean age, 34.79±8.16 years). Mean PSS scores significantly reduced from baseline to day 60 in group A and B (mean change, 38.6% and 41.6% respectively; p<0.0001). Sleep quality, happiness level, and eating behavior significantly improved from baseline to day 60 in groups A and B (p<0.0001). Serum cortisol level in group B was significantly reduced at day 60 (p<0.05). Both group A and B showed significant improvement in stress levels, sleep quality, happiness level, and eating behavior at day 60 (p<0.05) compared to group C. No safety concerns were reported. Conclusions: AshwaSR 150 mg and 300 mg capsules reduced perceived stress and improved sleep quality, eating behavior, and happiness levels and were safe in healthy adult, stressed subjects over 60 days of administration.

Abstract: Background: A remarkable increase in metabolic comorbidities occur in people living with HIV infection (PLWH). Supervised physical activity provides significant health benefits. Ginkgo biloba (GKB) extract has been reported to have a wide range of metabolic advantages. This study aimed to examine the effects of an exercise training (ET) program and a GKB extract on PLWH. Methods: This was a randomized placebo-controlled double-blind study. Twenty-eight PLWH were assigned to receive a placebo (n=10), GKB extract (n=10), or statins (n=8). All patients underwent a supervised ET program 3-5 times per week. Anthropometric measurements, functional capacity, and metabolic parameters were assessed in all participants at baseline and after 12 weeks of follow-up. Results: After the 12-week intervention, body fat decreased significantly by 2-3% in all groups relative to their baseline values (p&lt;0.05). Total cholesterol and LDL-c were significantly decreased in the ET+statin group (p= 0.04, and p= 0.007, respectively) compared to baseline values, while HbA1c and the HOMA-IR index were significantly decreased in the ET+GKB group (p= 0.03 and p= 0.02, respectively) compared to baseline values, and a significant increase in CD4+ T cell mean was observed in the ET+placebo group (p=0.005) compared to baseline values. A significant increase in cardiorespiratory capacity (VO2 max) from their baseline values was observed in all groups (p&lt;0.001) after 12-weeks of intervention from their baseline values. Conclusions: Body fat and cardiorespiratory fitness significantly improved after a 12-week supervised ET program. GKB extract significantly decreased insulin resistance. Future studies with larger sample sizes are required.

Abstract: Occupational Therapy provides a framework to develop and implement interventions to increase independence and functionality. Through the dynamic interaction between people tasks and environments, we facilitate meaningful participation in daily routines. These routines are categorized into key performance areas, ADLs, education, productive work, leisure, and social participation. Work-related capabilities – specific tasks, skills, and performance patterns – are a fundamental part of who we are and contribute to our health, well-being, and being active in life. The American Occupational Therapy Association (AOTA) Framework states that occupational therapists have the expertise to look at the whole person in their environment. This means Occupational Therapy is an evolving profession with a focus on many different aspects of human function. Occupational therapists are to teach skills for functional independence. Theoretical models in Occupational Therapy help to bridge theory and practice by organizing many theoretical concepts into frameworks for designing interventions. These models underpin the assessment and intervention processes used by therapists, guide the evaluations, and inform the therapy.

Abstract: Medicinal plants are widely used in bolivian folk medicine for the treatment of infectious diseases. We have selected one, Clinopodium bolivianum (Benth.) Kuntze, known as “Khoa”, to investigate its potential anti-HIV activity, since traditionally it has been used to treat other viral infectious diseases. We have carried out an antiviral bioassay-guided fractionation of different extracts of C. bolivianum. An antiviral crude polysaccharide was obtained, SBAS, rich in glucose, galactose, mannose, arabinose, xylose, rhamnose and only traces of galacturonic acid. SBAS exhibited antiviral activity with a mechanism of action unrelated to the mannose-lectin DC-SIGN receptors but with a strong viral neutralization activity. In summary, a purified polysaccharide from C. bolivianum have been identified as the main compound responsible of its antiviral activity. SBAs proved to be a neutralizing agent with high antiviral capacity in vitro, so it could be part of new microbicide formulations to prevent HIV transmission.

Abstract:

Long-lasting brain fatigue is a consequence of stroke or traumatic brain injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, and aging-related chronic low-grade inflammatory disorders. The pathogenesis of brain fatigue is linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, and ATP energy supply, which are associated with multiple molecular targets and signaling pathways in neuroendocrine-immune and blood circulation systems. Regeneration of damaged brain tissue is a long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic–catabolic homeostasis to recover harmonized sympathoadrenal system (SAS)-mediated function, brain energy supply, and deregulated gene expression in rehabilitation. The driving mechanism of spontaneous recovery and regeneration of brain tissue is a cross-talk of mediators of neuronal, microglia, immunocompetent, and endothelial cells collectively involved in neurogenesis and angiogenesis, which plant adaptogens can target. Adaptogens are small molecules of plant origin that increase the adaptability of cells and organisms to stress by interaction with the HPA-axis and SAS of the stress system (neuroendocrine immune and cardiovascular complex), targeting multiple mediators of adaptive GPCR signaling pathways. Two major groups of adaptogens comprise (i) phenolic phenethyl and phenylpropanoid derivatives and (ii) tetracyclic and pentacyclic glycosides, whose chemical structure can be distinguished as related correspondingly to (i) -monoamine neurotransmitters of SAS (epinephrine, norepinephrine, and dopamine), and (ii) - steroid hormones (cortisol, testosterone, and estradiol). In this narrative review, we discuss (i) the multitarget mechanism of integrated pharmacological activity of botanical adaptogens in stress overload, ischemic stroke, and long-lasting brain fatigue, (ii) - time-dependent dual response of physiological regulatory systems to adaptogens to support homeostasis in chronic stress and overload, and (iii) - dual dose depending reversal (hormetic) effect of botanical adaptogens. This narrative review shows that the adaptogenic concept cannot be reduced and rectified to the various effects of adaptogens on selected molecular targets or specific modes of action without estimating their interactions within the networks of mediators of the neuroendocrine-immune complex that, in turn, regulates other pharmacological systems (cardiovascular, gastrointestinal, reproductive systems) due to numerous intra- and extracellular communications and feedback regulations. These interactions result in polyvalent action and the pleiotropic pharmacological activity of adaptogens, essential for characterizing adaptogens as distinct types of botanicals. They trigger the defense adaptive stress response that leads to the extension of the limits of resilience to overload, inducing brain fatigue and mental disorders. For the first time, this review justifies the neurogenesis potential of adaptogens, particularly botanical hybrid preparation (BHP) of Arctic Root and Ashwagandha, providing a rationale for potential use in individuals experiencing long-lasting brain fatigue. The review provided insight into future research on network pharmacology of adaptogens in preventing and rehabilitating long-lasting brain fatigue following stroke, trauma, and viral infections.

Abstract:

Background: Nigella sativa L. (seeds) and Olea europaea L. (leaves) are widely utilized as food supplements and traditional herbal remedies to reduce hyperglycemia. Purpose: This study evaluated the efficacy of a commercial combination of Nigella sativa and Olea europaea aqueous extracts, marketed as Phytosucrophage (PSP), in managing type 2 diabetes mellitus (T2DM) in patients resistant to oral antihyperglycemic drugs (OADs). Study Design: A multicenter, observational cohort study was conducted involving 38 treatment-naïve T2DM patients and 282 patients resistant to OADs. Participants received a fixed-dose capsule containing 550 mg of PSP, administered twice daily for 12 weeks. Clinical efficacy was assessed by monitoring fasting blood glucose, glycosylated hemoglobin (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels, and evaluating functional symptoms. Results: PSP treatment significantly reduced fasting blood glucose and HbA1c levels. Additionally, it alleviated functional symptoms of T2DM without inducing adverse effects. Conclusions: The findings suggest that PSP is an effective and safe adjunctive therapy for reducing blood glucose and HbA1c levels in T2DM patients resistant to OADs. PSP also improved clinical symptoms associated with T2DM without causing notable adverse effects.

Abstract: Melatonin was primarily identified for its indispensable roles in animals. Recently, it has been described as a potent regulator of several physiological pathways in plants. In humans, it has shown effects in the prevention or as an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of the circadian rhythm, regulation of the immunological system, epilepsy control, reduced allergic reactions, delaying the aging process, diminishing hormones related to cancer, and delaying Alzheimer’s and Parkinson’s disease symptoms. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The outcome of clinical trials showed that it can present scavenging of free radicals (reducing reactive oxygen species) and inflammation (reducing the synthesis of inflammatory cytokines modulating the immune system. Moreover, it can minimize apoptosis, insulin resistance, blood pressure, LDL-c, body mass index, adipose tissue mass, waist circumference, adhesion molecules, endothelial impairment, plaque formation, and muscle atrophy. It can also reduce hyperleptinemia, alanine aminotransferase, and liver fat. These effects result in neuro and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, dermatitis, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may also be more cost-effective, less adverse, and more sustainable than synthetic; therefore, it is better than the typical already sold. However, more clinical trials should show adequate doses, formulation, and treatment time.

Abstract:

Background: Boscia senegalensis Pers.) Lam. Ex Poir (Capparaceae) (BS), is an evergreen, perennial woody shrub, or tree native to Sahel region in Africa. It is an important local food plant in Africa and widely exploited for its fruits and seeds. Aim of the Study: The objective of this study was to test the antihyperglycemic effect of BS ex-vivo an in vivo and the mechanism involve in the reduction of blood sugar. Materials and Methods: We studied the antihyperglycemic effect of aqueous extract of seeds of BS. The chemical composition of BS aqueous extract was determined using UHPLC-MS. The inhibition of intestinal glucose absorption was studied ex-vivo in mice using a short-circuit current technique. The antihyperglycemic of BS in vivo was assess using an oral glucose tolerance test (OGTT) in rat. Results: In preclinical studies, BS (5 µg/mL to 2 mg/mL) induced concentration-dependent inhibition of sodium-dependent glucose transport across isolated mouse jejunum. The maximal inhibition was obtained with 2 mg/mL and was represented more than 75 % of the effect of Phloridzine and IC50 was close to 477.53 ± 1.22 µg/mL. Chronic BS treatment improved glucose tolerance and reduced body weight without any toxic effect in rat. The major compound found in the aqueous extract of BS seed was Glucocapparin (methyl glucosinolates). Conclusion: The result shows that BS directly inhibits the intestinal absorption of glucose ex-vivo in mice and it improved glucose tolerance and body weight in rats after acute and chronic oral administration in vivo.

Abstract: Background: The traditional recipe of Cupidon of Pahouins (CP) is an age-old secret kept by the female healers of the Fang people in Central Africa for feminine intimate care. The most widely used formulation is composed of four plant extracts: Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg., Musanga cecropioides R.Br. ex Tedlie, Myrianthus arboreus P.Beauv., and Myrianthus arboreus P.Beauv. Aim of the Study: The first objective of this study was to test the antibacterial, antifungal, and antineoplastic effects of each plant extract alone, and then to test the combination of the most active extracts in a polyherbal formulation (PHF). The secondary objective was to assess the mechanism of action of the PHF. The third objective was to evaluate the clinical benefits of the new formulation (PHF) in a multicenter observational cohort study after the evaluation of side effects. Materials and Methods: Antibacterial and antifungal activities were evaluated using the agar dilution method. Protein synthesis inhibitors were used to target the mechanism of action of CP and its anticancer activity using the seed germination method. The rational formulation of the candidate CP was achieved using the functional approach. Transdermal passage of CP was measured using Franz diffusion chambers. Side effects on skin and eyes were assessed using skin and eye irritation tests. The clinical benefits of CP were evaluated after medical examination in an observational study involving a cohort of 451 patients suffering from different infectious diseases, such as vaginal and oral infections, as well as skin, eye, and ear infections. Results: The plant extracts used in the traditional formulation exhibited antibacterial and antifungal effects. The best results were obtained with Alchornea cordifolia and Musanga cecropioides, which were subsequently combined in a PHF to produce a new CP. On Gram-positive bacteria, CP was most effective against Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus warneri, Staphylococcus pettenkoferi Staphylococcus agalactiae, as well as Corynebacterium striatum. The same efficacy was observed on Gram-negative bacteria such as Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, Proteus mirabilis, and Salmonella spp. In addition, the effect of CP was synergistic on several microorganisms tested (FICI < 1). The new PHF exhibited antifungal activity against Candida albicans, as well as antineoplastic activity (IC50 = 2.92 ± 0.12 mg/mL). A positive clinical benefit was observed in humans following the use of CP. The phytodrug cleared infections of the skin, ears, eyes, vagina, and mouth, with no obvious adverse effects. Conclusion: This study confirms the efficacy of traditional PHF in treating or preventing bacterial and fungal infections. This study shows that alternative and combination poly-phytotherapy (ACP) can be used to improve the efficacy of traditional treatments.

Abstract: Background/Objectives: Whole-body cryotherapy (WBC) is widely recognized for its analgesic and anti-inflammatory effects. Despite growing interest in its therapeutic potential, the impact of WBC on functional performance, pain perception, sleep quality and quality of life among indi-viduals with multiple sclerosis (MS) remains underexplored. This study aimed to assess the ef-fects of a 10-session WBC protocol on functional and psychological parameters in patients with MS and compare them with individuals without neurological disorders. Methods: A total of 73 participants, divided into two groups: non-neurological individuals (non-MS, n=43) and patients with MS (MS, n=30), underwent 10 WBC sessions (-120 °C to -130 °C) over two weeks. Assess-ments included the Numerical Rating Scale (NRS), 30-Second Chair Stand Test (30CTS), Timed-Up-and-Go Test (TUG), and Pittsburgh Sleep Quality Index, WHOQOL-Bref conducted pre-treatment, post-treatment, and at 10-day follow-up. Results: In the MS group, significant im-provements were observed post-treatment in NRS, 30CTS, WHOQOL-1, and PSQI. However, only CTS and WHOQOL-3 maintained improvements during follow-up. In the non-MS group, statis-tically significant improvements were observed post-treatment across most parameters, except for NRS and WHOQOL-3, with most effects diminishing by follow-up. No deterioration in any assessed parameters was observed in either group. Conclusions: WBC demonstrates potential benefits for managing MS symptoms, particularly pain and sleep quality, with no observed dete-rioration in parameters and some effects emerging only during follow-up, underscoring its safety and the need for further research on long-term outcomes.

Abstract: Diabetes mellitus is a chronic non-communicable disease with increasing prevalence in Latin America and worldwide, impacting various social and economic areas. It causes numerous complications for those affected. Current treatments for diabetes include oral hypoglycemic drugs, which can lead to adverse effects and health complications. Other natural alternatives for DM treatment have been studied as adjunct therapies to reduce or eliminate the need for antidiabetic medications. Several natural supplements may offer an alternative to improve the quality of life for patients with DM and in nutraceutical applications. Due to their phenolic compound content, some leguminous substances have been proposed for these alternatives. Phenolic compounds, with their high antioxidant activity, have shown promising potential in insulin synthesis, secretion, and the functionality of the endocrine pancreas. This review provides valuable information on various leguminous plants with anti-diabetic properties, including antioxidant, hypoglycemic, anti-fat-induced damage, and anti-apoptotic properties in vitro and in vivo, attributed to their high content of phenolic compounds in seeds. Natural products with antidiabetic potential and pharmacological treatments improve diabetes management by offering more effective and complementary alternatives. To integrate these herbal remedies into modern medicine, further research on phenolic compound type, doses, efficacy, and safety in the human population.

Abstract: Immune checkpoints are essential for regulating excessive autoimmune responses and maintaining immune homeostasis. However, in the tumor microenvironment, these checkpoints can lead to cytotoxic T cell exhaustion, allowing cancer cells to evade immune surveillance and promote tumor progression. The expression of programmed death-ligand 1 (PD-L1) in cancer cells is associated with poor prognoses, reduced survival rates, and lower responses to therapies. Consequently, downregulating PD-L1 expression has become a key strategy in developing immune checkpoint inhibitors (ICIs). Caryophylli cortex (CC), derived from the bark of the clove tree Syzygium aromaticum, possesses antioxidant and cytotoxic properties against cancer cells, yet its potential as an ICI remains unclear. Therefore, we investigated whether CC extract modulates PD-L1 expression in cancer cells and assessed its ability to activate T cell immunity in both in vitro co-culture and in vivo animal models. The results indicated that CC extract significantly downregulated both constitutive and inducible PD-L1 expression at non-toxic concentrations for cancer cells while enhancing cancer cell mortality and T cell activity in co-culture. Additionally, administering CC extract to hPD-L1/MC-38 tumor-bearing mice resulted in over a 70% reduction in tumor growth and increased CD8+ T cell infiltration in the tumor microenvironment. Principal component analysis identified bergenin, chlorogenic acid, and ellagic acid as active ICIs. These findings suggest that CC extract exerts a potent antitumor effect as an immune checkpoint blocker by inhibiting PD-L1 expression in cancer cells and disrupting the PD-1/PD-L1 interaction.

Abstract: Plants and algae harbor diverse molecules with antioxidant activity that have been demonstrated to directly inhibit the growth of cancer cells and alleviate the oxidative damage side effects of certain antitumor therapies. Although supplementation with antioxidants alone or in combination with chemotherapy has shown promise in improving quality of life, further investigation is needed into the effects of antioxidant combinations on specific cancer cell lines. In this study, the in vitro cytotoxic and apoptotic properties of plant/algae natural compounds and dietary supplements were investigated on various human cancer cell lines, including bone, leukemia, colorectal, breast and prostatic cancers. Apple polyphenols, fucoxanthin, and plant tocotrienols exhibited cytotoxic effects across all lines, with tocotrienols particularly potent, showing a low half- inhibitory concentration (IC50) in bone cancer cells (4.3 μg/mL). Analysis of dietary supplements 2.1, 4.0 and 10.0, revealed that supplement 10.0 exhibited specific cytotoxic activity against the TIB-223 bone cancer line, with an IC50 of 126 μg/mL. Both tocotrienols and supplement 10.0, induced morphological changes, inhibited cell migration (anti-metastatic activity), and promoted apoptosis in TIB-223 cells, as demonstrated by caspase 3/7 activation. These findings provide valuable insights for the development of specific dietary supplements to enhance the anticancer effect of traditional chemotherapies for certain cancer types.

Abstract: Terminalia bellirica, and Terminalia chebula are significant botanicals in ancient Ayurvedic medicine. They are renowned for their therapeutic properties, notably in addressing gastrointestinal (GI) diseases. These plants have undergone thorough examination related to their antibacterial, anti-inflammatory, and antioxidant properties, which make them highly efficient natural treatments for controlling gastrointestinal infections. The current research demonstrated the antibacterial efficacy of fruit extracts of Terminalia bellirica, and Terminalia chebula against Bacillus cereus, Shigella sonnei, Shigella flexneri, and Salmonella typhimurium. We performed disc diffusion and liquid microdilution experiments to evaluate the antibacterial efficacy. All extracts of Terminalia bellirica and Terminalia chebula showed good antibacterial effects against B. cereus and S. flexneri. The minimum inhibitory concentration (MIC) values ranged from 94 µg/mL to 556 µg/mL. The methanol extracts from both plants also showed noteworthy antibacterial activity against S. sonnei and S. typhimurium, with MIC values of 755 µg/mL for both. Fractional inhibitory concentration studies revealed additive interactions between the extracts and conventional antibiotics when used concurrently. The phytochemical composition of T. bellirica and T. chebula extracts was analysed using liquid chromatography-mass spectrometry (LC-MS), which identified several tannins, including methyl gallate, propyl gallate, gallic acid, and ellagic acid. Lethality assays conducted using Artemia franciscana Kellogg nauplii indicated that all plant extracts are non-toxic. The antibacterial properties and absence of toxicity in T. bellirica and T. chebula fruit extracts indicate their potential for antibiotic development, warranting additional mechanistic and phytochemical studies.