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Abstract As a major component of innate immunity and a positive regulator of interferons, the Stimulator of interferon gene (STING) has an immunotherapy potential to govern a variety of infectious diseases. Despite the recent advances regarding vaccines against COVID-19, nontoxic novel adjuvants with the potential to enhance vaccine efficacy are urgently desired. In this connection, it has been well-documented that STING agonists are applied to combat COVID-19. This approach is of major significance for boosting immune responses most likely through an autophagy-dependent manner in susceptible individuals against infection induced by severe acute respiratory syndrome Coronavirus (SARS‑CoV‑2). Given that STING agonists exert substantial immunomodulatory impacts under a wide array of pathologic conditions, these agents could be considered novel adjuvants for enhancing immunogenicity against the SARS-related coronavirus. Here, we intend to discuss the recent advances in STING agonists’ recruitment to boost innate immune responses upon vaccination against SARS-related coronavirus infections. In light of the primordial role of autophagy modulation, the potential of being an antiviral vaccine adjuvant was also explored.

The coronavirus disease of 2019 (COVID-19) may be considered sepsis on the basis that all the pathological events and the subsequent organ-to-organ interaction in sepsis also occur in COVID-19. In this article, the authors first discussed the rationale for the use of vitamin C (Vit-C) in sepsis and septic patients. They also reviewed the role of a high dose of Vit-C in COVID-19, which included clinical trials designed for the management of this viral disease. Methods: The researchers explored databases of PubMed, Scopus, ISI Web of Science, and Google Scholar. Data were extracted to assess the effects of Vit-C in septic patients and also the efficacy of supplementation with a high dose of Vit-C regarding the clinical outcomes of patients with COVID-19. Results: Recent research findings indicate that severe inflammatory responses (cytokine storms) and oxidative stress are important causes for the high mortality in COVID-19 patients. It seems, however, that administering high doses of Vit-C can offer a therapeutic benefit. High doses of intravenous Vit-C, with its antioxidant properties and pleiotropic functions, could attenuate the tissue damage caused by excessive levels of free radicals following the cytokine storm and septic shock in severe cases of the disease. Conclusions: Recent literature suggests that high doses of Vit-C have a potential role in reducing mortality and intubation rates in critically ill COVID-19 patients. However, determining the optimal duration and dose of Vit-C in these patients requires further studies.

Background and aims: This article was written to better introduce Alcea rosea as a valuable medicinal plant to the medical and pharmaceutical communities and the general public for industrial and traditional uses as a valuable medicinal plant. Methods: The results were gathered from scientific papers and databases to find flavonoids, phenolic acids, amino acids, fatty acids, anthocyanins, polysaccharides, and pharmacological activities in A. rosea. Sixty-two articles were found, and 51 were used for our final results. Results: Studies have shown that flowers, roots, seeds, and other parts of the plant exert antioxidant, antimicrobial, anti-inflammatory, cytotoxic, sedative, analgesic and anti-cough effects due to the presence of valuable phytochemical compounds such as anthocyanins, pectin, starch, monosaccharide, disaccharide, mucilage, flavonoids (hypolaetin-8-glucoside, isoquercitrin, kaempferol, caffeic acid, p-coumaric acid), coumarins, scopolamine, phytosterol, tannins, asparagine, and certain amino acids. Conclusion: Alcea rosea, as a rich source of secondary metabolites, can have diverse applications in medical and food research.

Introduction: There is a global gap between tuberculosis incident cases and the notified cases. Active household contact investigation is one of the strategies to narrow this gap. It has the advantage of giving early diagnosis and preventive treatment to vulnerable and eligible groups. This study assessed the practice of contact investigation and tuberculosis preventive treatment adherence in central Ethiopia. Method: A cross-sectional study covering all registered bacteriologically confirmed pulmonary tuberculosis patients and their close contacts was conducted in central Ethiopia from January 1, 2022, to December 30, 2022. Result: A total of 1372 household contacts were declared by the index cases. From these 79.44 % (1090) contacts received a one-time tuberculosis screening giving a total of four (0.36 %) active TB cases. Among 484 household contacts of drug-resistant tuberculosis index cases, 5.53 % (14) had presumptive tuberculosis and 0.79 % (2) had active tuberculosis. While among 837 household contacts of drug-susceptible tuberculosis index cases presumptive TB cases were 1.91 % (16) and active TB cases were 0.23 % (2). Of the 142 eligible under 15 children 81.69 % (116) had started tuberculosis preventive treatment and 84.48 % (98) completed the treatment. On multivariable logistic regression, the associated factor for tuberculosis preventive treatment non-adherence was age 2–5 years (aOR, 0.02, 95 % CI (0.002–0.20) and age 5–15 years (aOR, 0.04,95 % CI (0.002–0 0.95)) P=

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD−FT+). The second group received SD without FT(SD+FT−). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SD−FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P

Isothiocyanates (ITCs) belong to a group of natural products that possess a highly reactive electrophilic −N=C=S functional group. They are stored in plants as precursor molecules, glucosinolates, which are processed by the tyrosinase enzyme upon plant tissue damage to release ITCs, along with other products. Isolated from broccoli, sulforaphane is by far the most studied antioxidant ITC, acting primarily through the induction of a transcription factor, the nuclear factor erythroid 2–related factor 2 (Nrf2), which upregulates downstream antioxidant genes/proteins. Paradoxically, sulforaphane, as a pro-oxidant compound, can also increase the levels of reactive oxygen species, a mechanism which is attributed to its anticancer effect. Beyond highlighting the common pro-oxidant and antioxidant effects of sulforaphane, the present paper was designed to assess the diverse anti-inflammatory mechanisms reported to date using a variety of in vitro and in vivo experimental models. Sulforaphane downregulates the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, cycloxyhenase-2, and inducible nitric oxide synthase. The signalling pathways of nuclear factor κB, activator protein 1, sirtuins 1, silent information regulator sirtuin 1 and 3, and microRNAs are among those affected by sulforaphane. These anti-inflammatory actions are sometimes due to direct action via interaction with the sulfhydryl structural moiety of cysteine residues in enzymes/proteins. The following are among the topics discussed in this paper: paradoxical signalling pathways such as the immunosuppressant or immunostimulant mechanisms; crosstalk between the oxidative and inflammatory pathways; and effects dependent on health and disease states.

Maytansine is a pharmacologically active 19-membered ansamacrolide derived from various medicinal plants and microorganisms. Among the most studied pharmacological activities of maytansine over the past few decades are anticancer and anti-bacterial effects. The anticancer mechanism of action is primarily mediated through interaction with the tubulin thereby inhibiting the assembly of microtubules. This ultimately leads to decreased stability of microtubule dynamics and cause cell cycle arrest, resulting in apoptosis. Despite its potent pharmacological effects, the therapeutic applications of maytansine in clinical medicine are quite limited due to its non-selective cytotoxicity. To overcome these limitations, several derivatives have been designed and developed mostly by modifying the parent structural skeleton of maytansine. These structural derivatives exhibit improved pharmacological activities as compared to maytansine. The present review provides a valuable insight into maytansine and its synthetic derivatives as anticancer agents.

Background and aims: Given the prevalence of urolithiasis and the popularity of black radish extract for the treatment of this problem, the present study was designed to investigate its effect in alkalizing urine in stone-forming patients referred to Imam Ali clinic in Shahrekord (Iran). Methods: In this clinical trial, the urine pH was measured along with the 24-hour urine assessment for urine volume and urine citrate, oxalate, calcium, uric acid, and creatinine levels of 20 patients before and after the intervention. Results: The results showed a significant increase (P < 0.001) in mean urine pH after the administration of Raphanus sativus syrup for 14 days. The mean 24-hour urine volume and citrate level increased significantly (P < 0.05). In addition, the mean uric acid and oxalate levels decreased significantly (P < 0.05). Mean changes in 24-hour urine creatinine and calcium levels were not statistically significant after intervention (P > 0.05). Conclusion: Raphanus sativus extract treatment can increase urine pH, urine citrate level, and urine volume and decreases uric acid and oxalate levels. Therefore, the plant may be used for the treatment and prevention of uric acid and cystine stones.

Abstract Background The existing drug treatments for trypanosomiases are limited and suffer from shortcomings due to their toxicity and the emergence of resistant parasites. Developing anti‐trypanosomal compounds based on natural products is a promising way of fighting trypanosomiases. Objectives This study aims to identify through scientific review a large variety of medicinal plants (anti‐trypanosomal) used worldwide and scientifically shown to display anti‐trypanosomal effects. Methods To collect data, the anti‐trypanosomal activities of Africa, Asia, the Middle East, South America, North America, Europe and Oceania medicinal plants have been checked by considering the published paper. Results Based on collected data, 77 natural molecules were reported in the literature. Of which 59 were from the African region, 11 from Asia, 3 from Europe and 4 from Latin America. These active components belong to alkaloids, triterpenoids, lactone, quinoids, flavonoids, iridoids, lignans, steroids, lipids, oxygenated heterocycles, benzenoids, proteins, coumarins, phenylpropanoids and peptides. We also specified the prosperous plants with unique anti‐trypanosomal activities. Conclusions However, there is a need for further studies on the ability of the isolated compounds to ameliorate the trypanosome‐induced pathological alterations and also the elucidation of their modes of actions and activities against other trypanosome species.

Rheumatic diseases and disorders (RDDs) are a group of chronic autoimmune diseases that are collectively called ''multicausal diseases''. They have resulted from predisposing genetic profiles and exposure to a range of environmental, occupational and lifestyle risk factors. Other causative factors include bacterial and viral attacks, sexual habits, trauma, etc. In addition, numerous studies reported that redox imbalance is one of the most serious consequences of RDDs. For example, rheumatoid arthritis (RA) as a classic example of chronic RDDs is linked to oxidative stress. This paper summarizes the contributions of redox imbalance to RDDs. The findings suggest that establishing direct or indirect therapeutic strategies for RDDs requires a more in-depth understanding of the redox dysregulation in these diseases. For example, the recent awareness of the roles of peroxiredoxins (Prdxs, e.g. Prdx2, Prdx3) in RDDs provided one potential route of therapeutic intervention of these pathologies. Changes in stressful lifestyles and dietary habits may also provide additional benefits in the management of RDDs. Future studies should be directed to explore molecular interactions in redox regulations associated with RDDS and potential therapeutic interventions.

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-β-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins’ antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica’s north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

Abstract Background In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. Main body SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. Conclusions Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

Objective: To assess the patient’s satisfaction rate during two distinct registry procedures in the emergency department. Methods: A cross-sectional study was conducted in educational hospitals with a high volume of patient’s admission in Tabriz-Iran and Erzurum-Turkey. In this study, we used a Press Ganey questionnaire as a data collection tool that was filled out with patients or their companions before discharging or referred to other areas (wards). Finally, data were analyzed by using SPSS software version 16. Results: The included patients were from three-admission time courses includes morning, evening, and night shifts. The present study results indicated that the total satisfaction score was two scores higher than the classic one (p

Abstract Background Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. Methods This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. Results With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). Conclusion The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. Trial registration The trial was registered as IRCT20190810044500N7 (19/09/2020).

Carnosic acid (CA) and carnosol (CAR) are two major diterpenes of the rosemary plant (Rosmarinus officinalis). They possess a phenolic structural moiety and are endowed with the power to remove cellular reactive oxygen species (ROS) either through direct scavenging reaction or indirectly through upregulation of antioxidant defences. Hand in hand with these activities are their multiple biological effects and therapeutic potential orchestrated through modulating various signalling pathways of inflammation, including the NF-κB, MAPK, Nrf2, SIRT1, STAT3 and NLRP3 inflammasomes, among others. Consequently, they ameliorate the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-1 and IL-6), adhesion molecules, chemokines and prostaglandins. These anti-inflammatory mechanisms of action as a therapeutic link to various effects of these compounds, as in many other natural products, are scrutinised.

The isolation of phlorizin from the bark of an apple tree in 1835 led to a flurry of research on its inhibitory effect on glucose transporters in the intestine and kidney. Using phlorizin as a prototype drug, antidiabetic agents with more selective inhibitory activity towards glucose transport at the kidney have subsequently been developed. In contrast, its hydrolysis product in the body, phloretin, which is also found in the apple plant, has weak antidiabetic properties. Phloretin, however, displays a range of pharmacological effects including antibacterial, anticancer, and cellular and organ protective properties both in vitro and in vivo. In this communication, the molecular basis of its anti-inflammatory mechanisms that attribute to its pharmacological effects is scrutinised. These include inhibiting the signalling pathways of inflammatory mediators’ expression that support its suppressive effect in immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal and lung injury, and inflammation in the gut, skin, and nervous system, among others.

Myrianthus arboreus is use traditionally as an antidiabetic agent in Ghana. We reported the in vivo antidiabetic activity of its 70 % ethanol stem bark extract (MAB) which we found to be strongly concentrated in its EtOAc fraction using glucose uptake and enzyme inhibitory assays. The present study sought to investigate the in vivo hypoglycaemic and anti-hyperlipidaemic activity of this ethyl acetate fraction of MAB (MAB-EtOAc, 50 and 100 mg/kg) in streptozotocin (STZ)-induced diabetic rats for 21 days, isolate and evaluate the bioactive constituents responsible for the antidiabetic activity. In silico pharmacokinetic and toxicity properties of the most active compound was also determined. MAB-EtOAc significantly (p < 0.001) reduced the blood glucose levels while normalizing considerably the altered serum lipid parameters of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Chemical investigation of MAB-EtOAc led to the isolation of seven known compounds including three flavanols which are reported for the first time in the plant: epicatechin (1), epigallocatechin (2), dulcisflavan (3), euscaphic acid (4), tormentic acid (5), sitosterol-3-O-β-d-glucopyranoside (6) and arjunolic acid (7). The compounds markedly inhibited the action of α-amylase and, except for 4 and 6, which stimulated considerably glucose uptake in C2C12 cells. Compounds 2, 3, 5, 6 and 7 which were further evaluated in STZ-induced diabetic rats demonstrated hypoglycaemic and anti-hyperlipidaemic activities which, however, were not comparable with MAB-EtOAc. Compound 3, the most active compound was predicted to be non-toxic, non-mutagenic, has reasonable oral bioavailability and a decent substrate for further drug development. The findings of this study show that the isolated compounds may contribute to the antidiabetic activity of M. arboreus and could serve as marker compounds for the quality control of herbal medicines that would be made from the plant.

Abstract Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.

Objective: To explore the potential insecticidal, ovipositor deterrent and antifeedant effects of ethyl acetate extract of the seeds of Senna tora (Syn. Cassia tora) against cowpea weevil (Callosobruchus maculatus). Methods: The activities were evaluated using standard protocols. In these bioassays, the cowpea seeds were used directly as an insect feed. The activity of the extract and isolated compounds were tested at concentrations of 100, 200 and 300 μg/mL and compared to neem oil and cinnamaldehyde (as standard positive controls). Phytochemical analysis of the ethyl acetate extract was done through a number of chromatographic techniques and the structures of the isolated compounds were established through comprehensive spectroscopic analysis including 2D-NMR and ESI-MS studies. Results: Fractionation of the active ethyl acetate extract resulted in the isolation of one known anthraquinone, aurantio-obtusin (1) and a novel compound that was named as cassiatorin (2). Compounds 1 and 2 showed comparable insect antifeedant properties with the positive controls while their insecticidal and ovipositor deterrent effects were far superior to the standard controls. Conclusions: It is thus concluded that Senna tora extracts and the isolated compounds (1 and 2) may be employed in the postharvest management of stored cowpea seeds and as other crop protectants.

Abstract Background The edible and medicinal leguminous plant Cassia tora L. (Fabaceae) is known to possess insecticidal properties against a wide range of plant-feeding insects. However, the bioactivity of extracts of this plant and their constituents against vectors of medical importance has been largely unexplored. We investigated the mosquito larvicidal activity of the seed extract and its major anthraquinones against larvae of the African malaria vector Anopheles gambiae (s.s.). Methods Third-fourth instar larval mortality was observed after 24, 48, 72 and 96 h of exposure to varying doses of the extracts, and two anthraquinones isolates identified using liquid chromatography- quadrupole time of flight mass spectrometry (LC-QtoF-MS). The mosquito larval mortality was evaluated relative to the natural insecticide azadirachtin. Results Fractionation of the crude extract decreased mosquito larvicidal activity, however, larvicidal activity increased with increasing dose of the treatment and exposure time. The known anthraquinones aurantio-obtusin and obtusin were identified as key larvicidal compounds. Aurantio-obtusin and obtusin, exhibited similar toxicity to larvae of A. gambiae (s.s.) with LD50 values of 10 and 10.2 ppm, respectively. However, the two anthraquinones were four- and ~ six-fold less potent than that of the crude seed extract and azadirachtin, which had comparable LD50 values of 2.5 and 1.7 ppm, respectively. Conclusion Both aurantio-obtusin and obtusin showed mosquito larvicidal activity which were comparable to their respective fractions although they were less potent relative to the crude extract and azadirachtin. Further studies need to be conducted on C. tora for its exploitation as a potential eco-friendly tool in mosquito larval source reduction.

Objective: To investigate the antioxidant, anti-α-glucosidase and pancreatic β-cell protective potential of Ensete superbum (E. superbum) seeds. Methods: A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, α-glucosidase assay and pancreatic β-cell (1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds. Results: The radical scavenging and reducing power effects comparable with the standard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of (38.2 ± 1.8) (n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin. Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic β-cell protection.

Liver diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are one of the major health challenges in the world and many conditions such as inadequate nutrition, viral infection, ethanol and drug abuse, xenobiotic exposure, and metabolic diseases have been implicated in the development and progression of liver diseases. Several factors including lipid peroxidation, production of reactive oxygen species (ROS), peroxynitrite formation, complement factors and proinflammatory mediators, such as cytokines and chemokines, are involved in hepatic diseases. Rosmarinic acid (RA) is a natural phenolic compound found mainly in the family Lamiaceae consisting of several medicinal plants, herbs and spices. Several biological activities have been reported for RA and these include antioxidant properties as a ROS scavenger and lipid peroxidation inhibitor, anti-inflammatory, neuroprotective and antiangiogenic among others. This review is aimed at discussing the effects of RA on the liver, highlighting its hepatoprotective potential and the underlying mechanisms.

The term “metabolic syndrome” (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting β cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS.

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target.

Coriolus versicolor (L.) Quél. is a higher fungi or mushroom which is now known by its accepted scientific name as Trametes versicolor (L.) Lloyd (family Polyporaceae). The polysaccharides, primarily two commercial products from China and Japan as PSP and PSK, respectively, have been claimed to serve as adjuvant therapy for cancer. In this paper, research advances in this field, including direct cytotoxicity in cancer cells and immunostimulatory effects, are scrutinised at three levels: in vitro, in vivo and clinical outcomes. The level of activity in the various cancers, key targets (both in cancer and immune cells) and pharmacological efficacies are discussed.

Berberine is a quaternary isoquinoline alkaloid that has been isolated from numerous plants which are still in use today as medicine and herbal supplements. The great deal of enthusiasm for intense research on berberine to date is based on its diverse pharmacological effects via action on multiple biological targets. Its poor bioavailability resulting from low intestinal absorption coupled with its efflux by the action of P-glycoprotein is, however, the major limitation. In this communication, the chemical approach of improving berberine’s bioavailability and pharmacological efficacy is scrutinised with specific reference to type-2 diabetes and associated diseases such as hyperlipidaemia and obesity. The application of modern delivery systems, research from combination studies to preparation of berberine structural hybrids with known biologically active compounds (antidiabetic, antihyperlipidaemic and antioxidant), as well as synthesis approaches of berberine derivative are presented. Improvement of bioavailability and efficacy through in vitro and ex vivo transport studies, as well as animal models of bioavailability/efficacy in lipid metabolism and diabetes targets are discussed.

The desperate need to find drugs for COVID-19 has indicated repurposing strategies as our quickest way to obtain efficacious medicines. One of the options under investigation is the old antimalarial drug, chloroquine, and its analog, hydroxychloroquine. Developed as synthetic succedanea of cinchona alkaloids, these chiral antimalarials are currently in use as the racemate. Besides the ethical concern related to accelerated large-scale clinical trials of drugs with unproven efficacy, the known potential detrimental cardiac effects of these drugs should also be considered. In principle, the safety profile might be ameliorated by using chloroquine/hydroxychloroquine single enantiomers in place of the racemate.

Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on cancer cell growth and metastasis have been established both in vitro and in vivo. The cellular targets that account to the anticancer effect of berberine are incredibly large and range from kinases (protein kinase B (Akt), mitogen activated protein kinases (MAPKs), cell cycle checkpoint kinases, etc.) and transcription factors to genes and protein regulators of cell survival, motility and death. The direct effect of berberine in cancer cells is however relatively weak and occur at moderate concentration range (10−100 µM) in most cancer cells. The poor pharmacokinetics profile resulting from poor absorption, efflux by permeability-glycoprotein (P-gc) and extensive metabolism in intestinal and hepatic cells are other dimensions of berberine’s limitation as anticancer agent. This communication addresses the research efforts during the last two decades that were devoted to enhancing the anticancer potential of berberine. Strategies highlighted include using berberine in combination with other chemotherapeutic agents either to reduce toxic side effects or enhance their anticancer effects; the various novel formulation approaches which by order of magnitude improved the pharmacokinetics of berberine; and semisynthetic approaches that enhanced potency by up to 100-fold.

Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect.

The study examined the comparative rutin contents and antioxidant potentials of the two closely related Moringa species: the Ethiopian (Moringa stenopetala) and Indian Moringa (M. oleifera). It is demonstrated that M. stenopetala leaves extract was a far superior (more than five-fold better) antioxidant than M. oleifera. Rutin was the principal constituent of M. stenopetala leaves while the compound was not detected in the leaves of M. oleifera. Quantitative HPLC-based analysis of M. stenopetala leaves revealed the rutin level at a respectable 2.34% ± 0.02% (on dry weight basis), which is equivalent to many commercial natural sources of this highly sought-after bioactive compound. Comparative analysis of rutin in some common herbal tea preparations of M. stenopetala leaves revealed that it is readily extractible with the highest amount obtained (98.8% ± 2.4%) when the leaves (1 g) were boiled in water (200 mL). For a large-scale exploitation of rutin, a fast and economically-viable isolation approach using solid phase extraction followed by crystallization or flash chromatography is outlined. Overall, the Ethiopian Moringa is distinctively different from the Indian Moringa and could be exploited as an industrial source of rutin for nutritional and/or medical uses.

In diverse living organisms, signaling within the cell, chemical communication between cells or simply the fate of cells to survive or die is largely dependent on the intricate balance of control mechanisms related to reactive oxygen species (ROS)[...]

The common buckwheat, Fagopyrum esculentum Moench (Polygonaceae) is a gluten-free pseudocereal that has been gaining in popularity in recent years as a low-calorie and nutrient-rich healthy food option. Buckwheat farming is common in Eastern European countries and the Far East, while in the UK and other Western European countries, the plant has limited medicinal or food applications. The vegetative parts, particularly the leaves and flowers, are among the best-known sources of the bioactive compound, rutin. Hence, functional foods originated from buckwheat leaves are common, although the scope of such applications is limited by phototoxicity associated with the fagopyrin composition. Here, the antioxidant and rutin composition of the leaves of the plant grown in the UK are assessed. The methanol extract of the leaves displayed a potent DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging effect along with reducing power. Quantitative High Performance Liquid Chromatography (HPLC)-based analysis showed the rutin content of the leaves as 3417 mg/100g (on dry weight (DW) basis). The identity of rutin was also confirmed by isolation and structural elucidation based on spectroscopic studies. From the chemical content analysis, including fagopyrin levels and the antioxidant assays, UK-grown buckwheat has potential as a commercial source of rutin or as a functional food.

Despite extensive progress in understanding the pathology of Alzheimer’s disease (AD) over the last 50 years, clinical trials based on the amyloid–beta (Aβ) hypothesis have kept failing in late stage human trials. As a result, just four old drugs of limited clinical outcomes and numerous side effects are currently used for AD therapy. This article assesses the common pharmacological targets and therapeutic principles for current and future drugs. It also underlines the merits of natural products acting through a polytherapeutic approach over a monotherapy option of AD therapy. Multi-targeting approaches through general antioxidant and anti-inflammatory mechanisms coupled with specific receptor and/or enzyme-mediated effects in neuroprotection, neuroregeneration, and other rational perspectives of novel drug discovery are emphasized.

Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity and old age. The main causes of T2DM are insulin resistance and/or inadequate insulin secretion. Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in T2DM, as its overexpression may induce insulin resistance. Thus, since PTP1B may be a therapeutic target for both T2DM and obesity, the search for novel and promising natural inhibitors has gained much attention. Hence, several marine organisms, including macro and microalgae, sponges, marine invertebrates, sea urchins, seaweeds, soft corals, lichens, and sea grasses, have been recently evaluated as potential drug sources. This review provides an overview of the role of PTP1B in T2DM insulin signaling and treatment, and highlights the recent findings of several compounds and extracts derived from marine organisms and their relevance as upcoming PTP1B inhibitors. In this systematic literature review, more than 60 marine-derived metabolites exhibiting PTP1B inhibitory activity are listed. Their chemical classes, structural features, relative PTP1B inhibitory potency (assessed by IC50 values), and structure⁻activity relationships (SARs) that could be drawn from the available data are discussed. The upcoming challenge in the field of marine research—metabolomics—is also addressed.

Citrus pomace is a huge agro-food industrial waste mostly composed of peels and traditionally used as compost or animal feed. Owing to its high content of compounds beneficial to humans (e.g., flavonoids, phenol-like acids, and terpenoids), citrus waste is increasingly used to produce valuable supplements, fragrance, or antimicrobials. However, such processes require sustainable and efficient extraction strategies by solvent-free techniques for environmentally-friendly good practices. In this work, we evaluated the antimicrobial and antibiofilm activity of water extracts of three citrus peels (orange, lemon, and citron) against ten different sanitary relevant bacteria. Both conventional extraction methods using hot water (HWE) and microwave-assisted extraction (MAE) were used. Even though no extract fully inhibited the growth of the target bacteria, these latter (mostly pseudomonads) showed a significant reduction in biofilm biomass. The most active extracts were obtained from orange and lemon peel by using MAE at 100 °C for 8 min. These results showed that citrus peel water infusions by MAE may reduce biofilm formation possibly enhancing the susceptibility of sanitary-related bacteria to disinfection procedures.

For centuries, plants have been exploited by mankind as sources of numerous cancer chemotherapeutic agents. Good examples of anticancer compounds of clinical significance today include the taxanes (e.g., taxol), vincristine, vinblastine, and the podophyllotoxin analogues that all trace their origin to higher plants. While all these drugs, along with the various other available therapeutic options, brought some relief in cancer management, a real breakthrough or cure has not yet been achieved. This critical review is a reflection on the lessons learnt from decades of research on the iridoid glycoside geniposide and its aglycone, genipin, which are currently used as gold standard reference compounds in cancer studies. Their effects on tumour development (carcinogenesis), cancer cell survival, and death, with particular emphasis on their mechanisms of actions, are discussed. Particular attention is also given to mechanisms related to the dual pro-oxidant and antioxidant effects of these compounds, the mitochondrial mechanism of cancer cell killing through reactive oxygen species (ROS), including that generated through the uncoupling protein-2 (UCP-2), the inflammatory mechanism, and cell cycle regulation. The implications of various studies for the evaluation of glycosidic and aglycone forms of natural products in vitro and in vivo through pharmacokinetic scrutiny are also addressed.

Iridoids are a class of monoterpenoid compounds constructed from 10-carbon skeleton of isoprene building units. These compounds in their aglycones and glycosylated forms exist in nature to contribute to mechanisms related to plant defenses and diverse plant-animal interactions. Recent studies have also shown that iridoids and other structurally related monoterpenes display a vast array of pharmacological effects that make them potential modulators of the Alzheimer’s disease (AD). This review critically evaluates the therapeutic potential of these natural products by assessing key in vitro and in vivo data published in the scientific literature. Mechanistic approach of scrutiny addressing their effects in the Alzheimer’s brain including the τ-protein phosphorylation signaling, amyloid beta (Aβ) formation, aggregation, toxicity and clearance along with various effects from antioxidant to antiinflammatory mechanisms are discussed. The drug likeness of these compounds and future prospects to consider in their development as potential leads are addressed.

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.