Clinical Toxicology of OTC Cough and Cold Pediatric Medications: A Narrative Review.

Cough and cold symptoms (CCS) are common pediatric conditions often treated with over-the-counter (OTC) medications. However, the available knowledge regarding the safety and toxicity of these medications in children is inadequate. Therefore, understanding their clinical toxicology is crucial for safeguarding children's well-being. This narrative review highlights the importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications for treating CCS in pediatric patients. The pharmacology, clinical features, and adverse effects of various drug classes commonly found in cough and cold medications are briefly discussed. Pharmacokinetic and pharmacodynamic parameters are also examined to understand the interactions between these drugs and the body. OTC cough and cold medications often contain active ingredients such as antihistamines, decongestants, antitussives, expectorants, and analgesics-antipyretics. The combination of multiple ingredients in these products significantly increases the risk of adverse effects and unintentional overdoses. Several case studies have reported significant toxicity and even fatalities associated with the use of these medications in children. This review underscores the critical importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications employed for treating CCS in pediatric patients. The findings highlight the significance of informed clinical practice and public health policies to ensure the well-being of children using OTC cough and cold medications.

The Nephroprotective Activity of Boesenbergia Rotunda Rhizome by Reducing Creatinine, Urea Nitrogen, Glutamic Pyruvic Transaminase, and Malondialdehyde Levels in the Blood and Attenuating the Expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 Genes in the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats.

Background: Cisplatin chemotherapy induces nephrotoxicity by producing reactive oxygen species, hence, discovering add-on nephroprotective drugs for patients with cancer is challenging. Boesenbergia rotunda has been reported for its antioxidant properties. Purpose: This study aims to explore the nephroprotective mechanism of the ethanol extract of Boesenbergia rotunda rhizome (EEBR) in cisplatin-induced rats. Methods: The rats were randomly assigned into 6 groups: the normal control (treated with saline); the negative control (cisplatin-induced without any treatment); the positive control (treated with quercetin 50 mg/kg BW); and 3 treatment EEBR (125 mg/kg BW; 250 mg/kg BW; 500 mg/kg BW) groups for 10 days. The % relative organ weight, kidney histopathology, and nephrotoxicity biomarkers expression were evaluated. Results: EEBR decreased creatinine, urea nitrogen, glutamic pyruvate transaminase, and malondialdehyde levels in the blood of cisplatin-induced rats. An insignificant increase in GOT was observed in rats treated with the highest dose of EEBR. EEBR did not significantly alter the BW and the % kidney relative weight. An abnormal shape of the Bowman capsule is observed in the negative control group. EEBR reduced the expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 genes in rats' kidneys. Conclusion: Boesenbergia rotunda could be considered a potential candidate for add-on therapy in cisplatin-treated patients, but further studies are needed to verify its efficacy and safety.

Formulation and Evaluation of Mucoadhesive Oral Care Gel Containing Kaempferia galanga Extract.

The rhizome of Kaempferia galanga (Zingiberaceae) is extensively used in traditional medicine by utilizing its various biological activities. It has been proven that ethyl-para-methoxycinnamate (EPMC) and other polyphenolic compounds are present in considerable amounts in the ethanolic extract of K. galanga rhizome (EKG). Our previous study confirmed that a dose of 0.5-1% of EKG demonstrated anti-inflammatory activity and a wound-healing effect in chemical-induced oral mucosal ulcers of Wistar rats. Currently, there are no reports on the formulation of oral gel containing EKG, thus revealing the potential of EKG to be developed as a herbal oral gel for mucosal ulcers. This study aims to formulate the best mucoadhesive oral care gel containing EKG in terms of physical stability. The presence of EPMC and the total phenols in the best EKG gel were also determined. The results revealed that Carbopol 934 is the best gelling agent for EKG gel preparations as proven by its stability during 14 days of storage. The statistical analysis resulted in a significant difference between the physical stability of the Carbopol 934-based EKG gel preparation compared to three commercial oral care gel products (p < 0.05). RP-HPLC chromatograms indicated that EPMC was identified in Carbopol 934-based gels containing 5% and 10% EKG at 6.056 and 6.146 min, respectively, with polyphenol levels of 1201.2557 mg/kg and 1849.1506 mg/kg, respectively. The hedonic test performed on 30 respondents to measure the degree of consumer acceptance and satisfaction confirmed that 5% EKG gel is the most sensorially accepted by the respondents. Data were analyzed using paired t-tests, one-way ANOVA, and a Kruskal-Wallis test. Taken together, the Carbopol 934-based gel containing 5% EKG could potentially be further developed as a topical anti-oral mucosal ulcer drug for clinical purposes.

Immunomodulatory Role of Plants and Their Constituents on the Management of Metabolic Disorders: An Evidence-Based Review.

The relationship between the immune system and metabolic diseases is complex and increasingly recognized as critical to understanding conditions like obesity, diabetes, and cardiovascular diseases. Modulation of the immune system in patients with metabolic disorders can offer several potential benefits. While the salutary impact of plant-derived bioactive compounds on metabolic and immune functions is acknowledged, there is a paucity of comprehensive reviews on the multifaceted and synergistic mechanisms through which these effects are mediated. This review elucidates the therapeutic potential of phytochemical formulations in ameliorating metabolic disorders and delineates their mechanistic implications on relevant biomarkers and immune modulation. Our analysis reveals a predominance of plant species, including Boswellia serrata, Cinnamomum cassia, Citrus bergamia, Coffea arabica, Ficus racemosa, Momordica charantia, Morus Alba, and Trigonella foenum-graecum, that have undergone clinical evaluation and have been substantiated to confer both metabolic and immunological benefits. The phytoconstituents contained in these plants exert their effects through a range of mechanisms, such as improving glucose regulation, reducing inflammatory responses, and modulating immune system. As such, these findings hold considerable promise for clinical and therapeutic translation and necessitate further empirical validation through randomized controlled trials and mechanistic elucidations to affirm the safety and efficacy of herbal formulations.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.

The pharmacology activities of Angelica keiskei Koidzumi and its efficacy and safety in humans.

Chronic exposure to elevated levels of pro-oxidant factors may cause structural failings at the mitochondrial DNA level and alteration of antioxidant enzymes (glutathione peroxidase, catalase, and superoxide dismutase). Oxidative stress is an imbalance between the capacity of endogenous non-enzymatic antioxidants (glutathione, alpha-lipoic acid, uric acid, ferritin, metallothionein, melatonin, and bilirubin) and the occurrence of pro-oxidant factors which may lead to the pathogenesis of various diseases that affects the kidneys, pancreas, central nervous system, and cardiovascular system. Therefore, the utilization of medicinal plants with antioxidant activity, e.g., Angelica keiskei Koidzumi which contains chalcones, is interesting to be explored. Chalcones exhibit direct and indirect antioxidant activity and prevent oxidative stress by decreasing ROS, RNS, and superoxide production. In this review, we discuss the pharmacology activities of A. keiskei Koidzumi and its efficacy in humans. The articles were explored on PubMed and Google Scholar databases and based on the titles and abstracts related to the topic of interest, and 55 articles were selected. Two main chalcones of this plant, 4-hydroxyderricin and xanthoangelol, have been reported for their various pharmacology activities. The efficacy of A. keiskei was confirmed in anti-obesity, hepatoprotective, anti-diabetes mellitus, and increasing plasma antioxidants in patients with metabolic syndrome. A keiskei is safe as proven by only mild or no adverse events reported, thus it is prospective to be further developed as an antioxidant nutraceutical.

Molecular dynamics study of stigmasterol and beta-sitosterol of Morinda citrifolia L. towards α-amylase and α-glucosidase.

Previous in vivo studies of Morinda citrifolia (Rubiaceae) reported that the extract inhibited α-amylase and reduced blood glucose levels in streptozotocin-induced diabetes mice. Moreover, molecular docking studies confirmed that ursolic acid and sterol compounds contained in the fruit interacted with important residues in the binding site of α-amylase and α-glucosidase. Our work aimed to study the complex stability of stigmasterol (which has been isolated from the M. citrifolia fruit for the first time) and beta-sitosterol towards α-amylase and α-glucosidase by employing molecular dynamics simulation on GROMACS 2016.3 embedded with the AMBER99SB-ILDN force field. The simulation was carried out for 100 ns at 310 oK. Based on the RMSD and RMSF graphs, the complexes of stigmasterol/α-amylase and stigmasterol/α-glucosidase are more stable compared to acarbose, the known inhibitor of both enzymes. Moreover, beta-sitosterol indicates a better stability complex with α-glucosidase compared to that of acarbose. Interestingly, the affinity of stigmasterol and beta-sitosterol to both enzymes, in terms of the total binding energy, is stronger than that of acarbose. Taken together, stigmasterol and beta-sitosterol in M. citrifolia fruit may have the potency to be developed as α-amylase and α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Pharmacology activity, toxicity, and clinical trials of Erythrina genus plants (Fabaceae): an evidence-based review.

The concept of using plants to alleviate diseases is always challenging. In West Java, Indonesia, a local plant, named dadap serep has been traditionally used to reduce blood glucose, fever, and edema, by pounding the leaves and applying them on the inflamed skin, or boiled and consumed as herbal tea. This plant belongs to the Erythrina genus, which covers approximately 120 species. The scope of this review (1943-2023) is related to the Global Development Goals, in particular Goal 3: Good Health and Wellbeing, by focusing on the pharmacology activity, toxicity, and clinical trials of Erythrina genus plants and their metabolites, e.g., pterocarpans, alkaloids, and flavonoids. Articles were searched on PubMed and ScienceDirect databases, using "Erythrina" AND "pharmacology activity" keywords, and only original articles written in English and open access were included. In vitro and in vivo studies reveal promising results, particularly for antibacterial and anticancer activities. The toxicity and clinical studies of Erythrina genus plants are limitedly reported. Considering that extensive caution should be taken when prescribing botanical drugs for patients parallelly taking a narrow therapeutic window drug, it is confirmed that no interactions of the Erythrina genus were recorded, indicating the safety of the studied plants. We, therefore, concluded that Erythrina genus plants are promising to be further explored for their effects in various signaling pathways as future plant-based drug candidates.

Molecular Docking Study of Phytosterols in Lygodium microphyllum Towards SIRT1 and AMPK, the in vitro Brine Shrimp Toxicity Test, and the Phenols and Sterols Levels in the Extract.

Background: Lygodium microphyllum is a fern plant with various pharmacological activities, and phytosterols were reported contained in the n-hexane and ethyl acetate extract of this plant. Phytosterols are known to inhibit steatosis, oxidative stress, and inflammation. Sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are the key proteins that control lipogenesis. However, information about L. microphyllum on SIRT1 and AMPK is still lacking. Purpose: This study aims to investigate the binding mode of phytosterols in L. microphyllum extract towards AMPK and SIRT1, and the toxicity of the extract against brine shrimp (Artemia salina) larvae, and to determine the phenols and sterols levels in the extract. Methods: The molecular docking was performed towards SIRT1 and AMPK using AutoDock v4.2.6, the toxicity of the extract was assayed against brine shrimp (Artemia salina) larvae, and the phytosterols were analyzed by employing a thin layer chromatography densitometry, and the total phenols were by spectrophotometry. Results: The molecular docking study revealed that ß-sitosterol and stigmasterol could occupy the active allosteric-binding site of SIRT1 and AMPK by binding to important residues similar to the protein's activators. The cold extraction of the plant yields 15.86% w/w. Phytochemical screening revealed the presence of phenols, steroids, flavonoids, alkaloids, and saponins. The total phenols are equivalent to 126 mg gallic acid (GAE)/g dry extract, the total sterols are 954.04 µg/g, and the ß-sitosterol level is 283.55 µg/g. The LC50 value of the extract towards A. salina larvae is 203.704 ppm. Conclusion: Lygodium microphyllum extract may have the potential to be further explored for its pharmacology activities, particularly in the discovery of plant-based anti-dyslipidemic drug candidates. However, further studies are needed to confirm their roles in alleviating lipid disorders.

Correlation between the Cognitive Status (SIRT1) and the Metabolic Function in Geriatric Patients Using the Indonesian Version of the Montreal Cognitive Assessment (MoCA-INA).

A growing life expectancy may result in a chronic medical condition and multimorbidity because the aging process leads to a decrease in cognitive and physiological function. These risks may affect the quality of life of geriatrics. The present study aims to determine the correlation between cognitive status (in terms of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent class III deacetylase) and metabolic function (in terms of the lipid profile, kidney function, and blood glucose) in geriatric patients. The differences in the parameters of metabolic function in the participants' cognitive status were determined by using the Indonesian version of the Montreal Cognitive Assessments (MoCA-Ina). The elderly participants (n = 120) were recruited at three sites in Indonesia from March to October 2022. Our study demonstrated a negative correlation between the cognitive status of geriatric patients and their metabolic function, represented by the MoCA-Ina score with a linear regression equation of y = 0.27 - 2.4 ×10-3x. Higher levels of LDL-C, cystatin C, and HbA1c were found in the Severe-Moderate Cognitive Impairment group. Determining the SIRT1 levels may be beneficial in predicting both the cognitive and metabolic status of geriatrics because this protein is among numerous metabolic sensors in the hypothalamus.

Pharmacological and Clinical Studies of Medicinal Plants That Inhibit Dipeptidyl Peptidase-IV.

Dipeptidyl peptidase IV (DPP-IV) is an enzyme responsible for the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1). DPP-IV plays a significant role in regulating blood glucose levels by modulating the activity of GLP-1. In the context of diabetes, DPP-IV inhibitors effectively block the activity of DPP-IV, hence mitigating the degradation of GLP-1. This, in turn, leads to an extension of GLP-1's duration of action, prolongs gastric emptying, enhances insulin sensitivity, and ultimately results in the reduction of blood glucose levels. Nonetheless, reported adverse events of DPP-IV inhibitors on T2DM patients make it essential to understand the activity and mechanism of these drugs, particularly viewed from the perspective of finding the effective and safe add-on medicinal plants, to be implemented in clinical practice. This review is intended to bring forth a thorough overview of plants that work by reducing DPP-IV activity, from computational technique, enzymatic study, animal experiments, and studies in humans. The articles were searched on PubMed using "Plants", "DPP-IV", "DPP-IV inhibitor", "GLP-1", "Type 2 diabetes", "diabetes", "in silico", "in vitro", "in vivo", "studies in human", "clinical study" as the query words, and filtered for ten years of publication period. Eighteen plants showed inhibition against DPP-IV as proven by in silico, in vitro, and in vivo studies; however, only ten plants were reported for efficacy in clinical studies. Several plant-based DPP-IV inhibitors, eg, Allium sativum, Morus Alba, Curcuma longa, Pterocarpus marsupium, and Taraxacum officinale, have established their functional role in inhibiting DPP-IV and have proven their effectiveness through studies in humans earning them a prominent place in therapeutic discovery.

Chitin Extracted from the Shell of Blue Swimming Crabs (Portunus pelagicus Linn.) Inhibits NF-kappaB p65 in Ethanol-Induced Gastric Ulcerative Wistar Rats.

Peptic ulcer disease is generated by the activation of NF-kappaB activity. A recent clinical study reported a significant increase in NF-kappaB2 gene expression in 79 samples of peptic ulcer patients compared to the control group. Moreover, the deacetylated chitin could alter the translocation of NF-kappaB p65 to the nucleus. Considering this, our work aims to explore the effect of chitin extracted from the shell of blue swimming crabs (Portunus pelagicus Linn.) towards NF-kappaB p65 levels in ethanol-induced gastric ulcerative Wistar rats. The shells are found abundantly as the waste of seafood processing in the northern part of West Java, Indonesia. In this study, chitin extraction was carried out using the microwave-assisted extraction method by employing choline chloride (C5H14ClNO) and DL-malic acid (C4H6O5) as the solvents. The inhibitory activity assay of chitin on the expression of NF-kappaB p65 was performed by using Western blot. The extraction yielded a good quality of chitin with a deacetylation degree of 30.8026%, molecular weight of 3.35 × 105 Da, and a negligible heavy metals level. Moreover, chitin extract at doses of 150, 300, and 600 mg/kg BW significantly reduced the percentage of gastric ulcer index compared to the negative control group. Meanwhile, chitin extract at doses of 300 and 600 mg/kg BW significantly inhibited NF-kappaB expression compared to the negative control group. Histopathological examination demonstrated a decrease in the number of necrotic cells and fat degeneration in the gastric mucosa and an increase in normal cells. Taken together, chitin extract obtained from the shells of blue swimming crabs may be able to prevent gastric ulcers induced by ethanol via the inhibition of NF-kappaB p65; however, further studies are needed to verify its anti-ulcerative properties.

Review of the Case Reports on Metformin, Sulfonylurea, and Thiazolidinedione Therapies in Type 2 Diabetes Mellitus Patients.

Type 2 diabetes mellitus (T2DM) is the world's most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic ß-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic ß-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of ß-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords 'metformin OR sulfonylureas OR thiazolidinediones AND case reports', filtered to 'free full text', 'case reports', and '10 years publication date'. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Healthy mitochondrial DNA in balanced mitochondrial dynamics: A potential marker for neuro­aging prediction (Review).

The mitochondrial genome or mitochondrial DNA (mtDNA) is released as a response to cellular stress. In mitochondrial biogenesis, active communication between the mitochondria genome and nucleus is associated with the mtDNA profile that affects the mitochondrial quality. The present review aimed to assess the molecular mechanism and potential roles of mitochondria in neuro-aging, including the importance of evaluating the health status of mtDNA via mitochondrial dynamics. The normal condition of mitochondria, defined as mitochondrial dynamics, includes persistent changes in morphology due to fission and fusion events and autophagy-mitophagy in the mitochondrial quality control process. The calculated copy number of mtDNA in the mitochondria genome represents cellular health, which can be affected by a long-term imbalance between the production and accumulation of reactive oxygen species in the neuroendocrine system, which leads to an abnormal function of mitochondria and mtDNA damage. Mitochondria health is a new approach to discovering a potential indicator for the health status of the nervous system and several types of neurodegenerative disorders. Mitochondrial dynamics is a key contributor to predicting neuro-aging development, which affects the self-renewal and differentiation of neurons in cell metabolism. Neuro-aging is associated with uncontrolled mitochondrial dynamics, which generates age-associated diseases via various mechanisms and signaling routes that lead to the mtDNA damage that has been associated with neurodegeneration. Future studies on the strategic positioning of mtDNA health profile are needed to detect early neurodegenerative disorders.

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors.

In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10-20% of these survivors have been reported to encounter long-term health problems, defined as 'long COVID-19', e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence. At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation. Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.

Clinical Toxicology of Vitamin D in Pediatrics: A Review and Case Reports.

Intoxication of vitamin D is not a common case in pediatrics. Vitamin D supplements are sold as OTC drugs; however, there is a lack of public education about the permissible limits of vitamin D intake which may lead to vitamin D toxicity (VDT). This review aims to give insights to readers or practitioners about the clinical toxicology of vitamin D in pediatrics, which includes the mechanism of VDT, case reports, and the management of vitamin D poisoning. VDT refers to serum 25(OH)D levels, particularly when the level exceeds 100 ng/mL (250 nmol/L) or is defined as hypervitaminosis D. Hypercalcemia is a common condition of vitamin D toxicity. Vitamin D and its metabolites in moderate levels can induce hypercalcemia, as indicated by the elevation of osteoclastic bone resorption, the presence of calcium in renal tubules, intestinal calcium intake (through increased production of calcium-binding protein in enterocytes), and the decrease of parathyroid hormone synthesis. VDT in pediatrics can be managed by discontinuing vitamin D intake; using activated charcoal, furosemide, prednisone, and calcitonin; rehydration using intravenous sodium chloride 0.9%; and dextrose fluid therapy. It is important for parents to be more careful when providing vitamin D to their children.

Efficacy and Safety of Add-On Plant-Based Drugs for COVID-19 Patients: A Review of the Randomized Control Trials.

COVID-19 caused by the infection of SARS-CoV-2 is still a global concern. WHO reported that from 13 March to 9 April 2023, there were 3 million new cases and approximately 23,000 deaths, mostly occurring in the South-East Asia and Eastern Mediterranean regions, which is predicted due to the new Omicron variant, Arcturus XBB.1.16. Many studies have reported the potency of medicinal plants in enhancing the function of the immune system to combat virus infection. The literature review aimed to describe the efficacy and safety of add-on plant-based drugs for COVID-19 patients. The articles were explored on the PubMed and Cochrane Library databases, and published during 2020-2023. Twenty-two varieties of plants were used as add-on therapy for COVID-19 patients. These plants were Andrographis paniculata, Viola odorata, Withania somnifera, Zingiber officinale, Curcuma longa, Ferula foetida, Centella asiatica, Thymus vulgaris, Citrus sinensis, Eugenia caryophyllus, Boswellia carterii, Elettaria cardamomum, Salvia rosmarinus, Piper nigrum, Alstonia scholaris, Picrorhiza kurroa, Swertia chirata, Caesalpinia crista, Cucurbita maxima, Tinospora cordifolia, Ocimum sanctum, and Allium sativum. The best efficacy of an add-on therapy for COVID-19 patients was found in A. paniculata herbs as a single component in pharmaceutical dosage form or in combination with other plants. The safety of the plant has been confirmed. A. paniculata does not show interaction with remdesivir or favipiravir, however, caution and therapy drug monitoring is needed if A. paniculata is used in combination with lopinavir or ritonavir because a strong noncompetitive inhibition of CYP3A4 may occur.

Role of the AMPK/SIRT1 pathway in non­alcoholic fatty liver disease (Review).

Non­alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP­activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

Cytotoxicity, Apoptosis, Migration Inhibition, and Autophagy-Induced by Crude Ricin from Ricinus communis Seeds in A549 Lung Cancer Cell Lines.

BACKGROUND Ricin protein derived from Ricinus communis seeds is known to have a high toxicity to humans and animals. Several studies revealed that ricin, belonging to ribosome inactivating protein-I, has cytotoxic properties against various types of cancer cell lines. MATERIAL AND METHODS Crude ricin (CR) from the seeds of R. communis was investigated for its cytotoxicity on the A549 cancer cell lines using the MTS assay, and the cell death mechanism was explored using flow cytometry and Western blot methods. The cell migration was measured using a scratch/wound-healing method and the autophagy activity was explored using Western blotting. RESULTS CR showed cytotoxicity against A549 cancer cell lines, with an IC50 of 40.94 ppm. CR induced apoptosis and necrosis, but apoptosis occurred more frequently than necrosis. Apoptosis induced by CR was mediated by the activation of caspase-9 and caspase-3. CR inhibited cell migration in a concentration- and time-dependent manner, with the highest effect occurred at the concentration of 1.0 ppm. The autophagic experiment showed that CR inhibited autophagy in A549 lung cancer cells by decreasing Beclin-1 levels while increasing Atg5 levels in a concentration-dependent manner and CR decreased LC3-II level while increasing p62 level. Cisplatin treatment also inhibited autophagy as it exhibited the same effect on those autophagic proteins as CR. CONCLUSIONS Our findings suggest that CR might be a potential candidate for anticancer drugs, but further study is needed to verify its anticancer properties.

Inhibitory activity of xanthoangelol isolated from Ashitaba (Angelica keiskei Koidzumi) towards α-glucosidase and dipeptidyl peptidase-IV: in silico and in vitro studies.

In Indonesia, the sap of Angelica keiskei Koidzumi has been utilized traditionally as a blood-sugar reducer, nonetheless, its molecular mechanism still needs to be studied. This study aimed to isolate xanthoangelol (XA) from the yellow sap of A. keiskei planted in Mount Rinjani, Indonesia, and to investigate its mechanism by in silico and in vitro methods towards α-glucosidase and dipeptidyl peptidase-IV (DPP-IV). The dried yellow sap was macerated using ethanol, subjected to liquid-liquid extraction using a different polarity of solvents, further gradient-eluted with column chromatography. The isolated compound, formed as yellow crystals, melting point 114-114.4 °C, λmax 368 nm, m/z 393.20 [M + H]+, was confirmed as XA. Acarbose, an α-glucosidase inhibitor, and sitagliptin, a DPP-IV inhibitor, respectively, were employed as the reference drugs for both the in silico and in vitro studies. XA interacts with essential amino acid residues 232-237 in the N-terminal N-loop of α-glucosidase by forming a hydrogen bond with Ala234, a salt-bridge with Asp232, and 9 hydrophobic interactions (binding energy -7.81 kcal/mol; Ki = 1.99 µM). These binding modes resemble those of acarbose. Moreover, XA forms hydrogen bonds with Glu205 and Glu206 in the subsite S2 and π-π interaction with Phe357 in the extensive subsite S2 of DPP-IV (binding energy -8.34 kcal/mol; Ki = 0.873 µM), which are similar to those of sitagliptin. XA inhibits both α-glucosidase (IC50 XA = 14.45 µM; IC50 acarbose = 207 µM) and DPP-IV (IC50 XA = 10.49 µM; IC50 sitagliptin = 0.87 µM). Taken together, XA isolated from the yellow sap of A. keiskei Koidzumi might possess the potential to be further developed as an inhibitor of α-glucosidase and DPP-IV.