Active Ingredients Research Articles

Efficacy and Safety of Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: Post Hoc Analysis by Baseline Disease Severity

Introduction: Clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) is the only triple-combination topical treatment approved for acne. These analyses assessed efficacy and safety of CAB gel by baseline acne severity vs component dyads and branded ADAP/BPO gel. Methods: These post hoc analyses used data pooled from two phase 2 and two phase 3, double-blind, 12-week studies (NCT03170388, NCT04892706, NCT04214639, NCT04214652). Eligible participants aged ≥9 years (≥12 years in NCT04892706) were randomized to once-daily CAB or vehicle gel. One phase 2 study included dyad combinations of CAB’s active ingredients: ADAP/BPO, CLIN/BPO, and CLIN/ADAP. The other phase 2 study included a head-to-head comparison of CAB gel and branded ADAP 0.3%/BPO 2.5% gel. Efficacy assessments included least-squares mean percent change from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin). Safety assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. Participants were categorized by baseline disease severity: moderate (EGSS = 3; n=1557) or severe (EGSS = 4; n=230). Results: After 12 weeks, inflammatory lesion reductions in participants with moderate acne were significantly greater with CAB (77.1%) than vehicle (54.1%; P<0.001), the 3 dyads (range, 64.4-69.4%; P≤0.001, all), and branded ADAP/BPO (72.8%; P<0.05). In the severe group, inflammatory lesion reductions with CAB (74.5%) were significantly greater than vehicle (44.4%; P<0.001) and 2 dyads (ADAP/BPO 63.9%, CLIN/BPO 61.3%; P<0.05), and similar to branded ADAP/BPO and CLIN/ADAP (75.4%/73.7%). Reductions in inflammatory lesions were greater than noninflammatory. Over half of CAB-treated participants with moderate disease achieved treatment success at week 12 (53.9% vs 19.5% vehicle; P<0.001), significantly greater than approximately one-third treated with dyads (range, 31.5-35.3%) or branded ADAP/BPO (38.1%; P≤0.001, all). Only CAB and CLIN/ADAP demonstrated significantly greater treatment success rates than vehicle in participants with severe acne at week 12 (30.9% and 34.0% vs 9.0%, respectively, P<0.05). Across all groups, most TEAEs were of mild to moderate severity. Mean cutaneous safety/tolerability scores were ≤1 (1 = mild) across severity groups. Conclusions: CAB gel demonstrated efficacy and safety in participants with both moderate and severe acne. Acne improvements with CAB were superior to the 3 dyads tested and branded ADAP/BPO in participants with moderate acne and generally numerically greater in participants with severe acne. To our knowledge, these analyses of combination topical acne treatments include data from the only double-blind, vehicle-controlled, head-to-head study to date. Funding: Ortho Dermatologics.

Вплив червоного та синього електромагнітного випромінювання на каталазну активність зародків в’юна Misgurnus fossilis L.

Photobiomodulation therapy is widely used to treat various pathological conditions. This therapy is based on the use of monochromatic light radiation. The light of the visible spectrum induces different biological effects at the molecular and cellular levels, both therapeutic and toxic. The obtained effect depends on the length of radiation, exposure, etc. One of the possible mechanisms of such influence is the regulation of pro-oxidant-antioxidant homeostasis. In order to clarify the mechanism of action of electromagnetic radiation (EMR) of different spectral composition, catalase (CAT) activity was investigated in germ cells of loach Misgurnus fossilis L. during embryogenesis. Since, loach embryos are an adequate system that reflects the physiological state of the cell both under normal conditions and as a result of the influence of various pharmacological, physical and chemical agents. The resulting zygotes were irradiated (10 min) with blue and red LEDs (λ = 460 and 660 nm, respectively). The activity of CAT was determined by the ability of hydrogen peroxi­de to form a stable colored complex with molybdenum salts. It was established that EMR of the red spectrum has the most pronounced biological effects and caused significant changes in catalase activity during embryogenesis relative to control and blue light. The maximum increase of the indicator occurs at the stage of 16 blastomeres, and at the stage of 8 and 10 divisions, a gradual decrease in enzymatic activity is observed. Irradiation by the light of the blue spectrum lasting 10 min did not cause significant changes in catalase activi­ty relative to the control at the early stages of loach embryogenesis. The obtained results suggest that CAT, one of the key enzymes of the antioxidant defense system, undergoes photoactivation under the influence of red light.

New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease

AbstractFerroptosis is a distinctive process of cellular demise that is linked to amino acid metabolism, lipid oxidation, and iron oxidation. The ferroptosis cascade genes, which are closely associated with the onset of lung diseases, are among the regulatory targets of nuclear factor erythroid 2-related factor 2 (Nrf2). Although the regulation of ferroptosis is mostly mediated by Nrf2, the precise roles and underlying regulatory mechanisms of ferroptosis and Nrf2 in lung illness remain unclear. This review provides new insights from recent discoveries involving the modulation of Nrf2 and ferroptosis in a range of lung diseases. It also systematically describes regulatory mechanisms involving lipid peroxidation, intracellular antioxidant levels, ubiquitination of Nrf2, and expression of FSP1 and GPX4. Finally, it summarises active ingredients and drugs with potential for the treatment of lung diseases. With the overarching aim of expediting improvements in treatment, this review provides a reference for novel therapeutic mechanisms and offers suggestions for the development of new medications for a variety of lung disorders.

A Journey Along the Boulevard of Bioactive Compounds from Natural Sources, with Cosmetic and Pharmaceutical Potential: Bee Venom, Cobra Venom, Ficus carica

Animal venom and plant extracts have been used since ancient times in traditional medicine worldwide. Natural components, valued for their safety and effectiveness, have been consistently used in cosmetic and pharmaceutical applications. We propose a journey along the boulevard of active compounds from natural sources, where bee venom (BV), cobra venom (CV), and Ficus carica reveal their individual therapeutic and cosmetic properties. The originality of this review lies in exploring the synergy of these bioactive sources, an approach that has not been presented in the literature. Although BV, CV, and Ficus carica have different origins and compositions, they have multiple common pharmacological and cosmetic actions, which make them ideal for inclusion in various products that can be used for skin care and health in general. Their anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, neuroprotective, and regenerative properties give them an essential role in the creation of potential innovative and effective products in the pharmaceutical and cosmetics industry. Although many plant extracts have antioxidant and anti-inflammatory properties, Ficus carica was chosen due to its complex biochemical composition, which provides valuable benefits in skin regeneration and protection against oxidative stress. According to the International Nomenclature of Cosmetic Ingredients (INCI), Ficus carica is used in the form of an extract of fruits, leaves, juice, bark or stem, each having specific applicability in topical formulations; due to the diversity of bioactive compounds, it can amplify the effectiveness of BV and CV, helping to enhance their beneficial effects and reducing the risk of adverse effects, due to its well-tolerated nature. Thus, this combination of natural ingredients opens up new perspectives in the development of innovative products, optimizing efficiency and maintaining a favorable safety profile. In this context, due to the reported experimental results, the three natural sources caught our attention, and we conceived the present work, which is a review made following the analysis of the current progress in the study of the bioactive compounds present in BV, CV, and Ficus carica. We focused on the novelties regarding pharmacological and cosmetic actions presented in the literature, and we highlighted the safety profile, as well as the modern approaches regarding the delivery and transport systems of the active substances from the three natural sources, and we evaluated their prospects in therapeutic and cosmetic use. This paper not only expands our knowledge of bioactive compounds, but it can also generate new ideas and motivations for the research and development of innovative treatments and skincare methods.

Determination of Osmium and other Platinum Group Elements in Active Pharmaceutical Ingredients by ICP-MS

Determination of Osmium and other Platinum Group Elements in Active Pharmaceutical Ingredients by ICP-MS

The Safety, Tolerability, and Pharmacokinetics of Active Ingredients From Hydroxysafflor Yellow A in Healthy Chinese Volunteers

AbstractHydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts. Part A was a randomized, double‐blind, placebo‐controlled dose‐escalation study that evaluated safety and tolerability. This included a single‐dose study with 7 dose levels of HSYA (6.25, 12.5, 25, 50, 75, 100, and 125 mg) in 52 volunteers, and a multidose study (100 and 125 mg) in 16 volunteers. Part B was an open‐label study where 12 volunteers received 75 mg of HSYA once daily for 14 consecutive days to examine PKs. There were no adverse events (AEs) leading to treatment discontinuation by HSYA throughout the treatment period. All reported AEs were mild and did not require special treatment. PK analysis revealed rapid absorption (median Tmax of 1.1 hours) and elimination (median t1/2 4.0 and 4.7 hours) of HSYA. Total body clearance on the 1st and 14th days was 1.7 and 1.6 L/h, respectively.

Formulation and Evaluation of Herbal Mouth Wash

The importance of oral and dental hygiene has been known from the beginning of civilization to the 21st century. Patients and dentists are faced with a wide variety of mouthwash products containing a variety of active and inactive ingredients. Making an informed decision about the suitability of a particular product for a particular patient can be a complex task. Many popular herbal products help fight plaque and periodontal disease, but they have only been used for a short time and only as an adjunct to other oral hygiene measures such as brushing and flossing. Natural mouthwashes may offer significant advantages over chemical mouthwashes. If a mouthwash can be developed using natural products that can be easily prepared at home and is safe to use, it could lead to an improvement in people's overall dental health. A variety of natural ingredients and materials have been used in this study. Thin layer chromatography was then performed to confirm the quality of the materials used. Subsequently, physical evaluation, pH measurement, stability studies, thin layer chromatography and antibacterial studies were carried out. The study concluded that the developed herbal mouthwash is a significant, therapeutically effective and suitable drug delivery agent with undoubtedly high potential, albeit at a low cost. Therefore, increased use of herbal preparations is necessary to avoid side effects. This study is an attempt to outline natural substances that can be used as effective mouthwashes.

Abstract A035: Infection of primary mammary fibroblasts with cytomegalovirus coordinately increases autotaxin-lysophosphatidate-inflammatory signaling, which could increase breast cancer metastasis

Abstract Background: Metastatic breast cancer is the most prevalent cause of mortality by cancer-related deaths in women. Our group showed that the 63% of Canadian breast cancer patients who were infected with CMV were 5.6-times more likely to develop Stage IV cancers with reduced relapse-free survival. Also, the metastatic phenotype of breast tumors and the number and sizes of lung metastases were increased in mice with latent infections. Fibroblasts are important sites of CMV infection. Cancer-associated fibroblasts (CAFs) are also major sites of autotaxin (ATX) secretion in breast tumors, whereas ATX production and CMV infection in breast cancer cells is negligible. ATX produces lysophosphatidate (LPA), which increases inflammatory cytokine production that stimulates further ATX secretion in a feedforward cycle. LPA promotes breast tumor growth and metastasis by signaling through six G protein-coupled receptors. Signaling is terminated by lipid phosphate phosphatases (LPPs)-1 and -3, which degrade LPA and are decreased in breast tumors. Hypothesis: Breast cancer metastasis could be increased by active CMV infection of CAFs through increased inflammation and LPA signaling. Results: Quiescent fibroblasts isolated and cultured from mammary tissue of non-tumor bearing mice (n>3) produced negligible quantities of ATX. LPA signaling was coordinately promoted in these primary fibroblasts infected for 48 h with 1 MOI of mouse CMV (n=3) with a 5-fold increase in mRNA for ATX (p=0.008), increased mRNAs for LPA2,3,4 receptors (p<0.05) and decreased mRNA expressions for LPP1 and LPP3 (p<0.05). An increase in the secretion of granulocyte monocyte-colony stimulating factor of 548 pg/ml (p=0.01) and Interleukin-6 by 8307 pg/ml (p=0.03) was observed post infection (n=5), thus creating a pro-inflammatory environment. Increased mRNA expression of fibroblast markers, including alpha-smooth muscle actin (p=0.005), fibroblast-associated protein (p=0.007), epidermal growth factor receptor (EGFR) (p=0.001) and transforming growth factor- ß receptor 1 (TGF-ßR1) (p=0.03) was also observed post-infection (n=3). The results were analyzed by student’s t-test. Assessment of these factors in breast cancer patients (n=1100) using the Tumor Immune Estimation Resource Analysis showed a positive correlation in the expression of EGFR and TGF-ßR1 with the LPA3,4 receptors (p<0.05). Conclusion: The changes in expression of ATX, LPA receptors and LPPs in CMV- infected fibroblasts are consistent with increased metastasis. Our results show that mCMV infection of primary mammary fibroblasts dramatically reprograms them to express CAF-like properties and promotes ATX-LPA-inflammatory signaling. CAFs are a major constituent of the tumor stroma. They promote tumor progression by secreting factors such as ATX, which increases metastasis, fibrosis and favors immunosuppression. Our results support the use of pharmacological agents to block signaling by the ATX-LPA-inflammatory cycle to treat breast and other cancers, especially for the majority of patients who are infected with CMV. Citation Format: Humayara Khan, Xiaoyun Tang, Frank Wuest, David N. Brindley, Denise G. Hemmings. Infection of primary mammary fibroblasts with cytomegalovirus coordinately increases autotaxin-lysophosphatidate-inflammatory signaling, which could increase breast cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A035.

A IMPORTÂNCIA DE ATIVOS NATURAIS NAS FORMULAÇÕES DE SKINCARE

INTRODUCTION: This study investigates the effectiveness of natural products in skincare beyond their aesthetic function, exploring their therapeutic properties for skin care. The analysis focuses on active ingredients such as Aloe Vera and essential oils from the Amazon, highlighting their antioxidant, anti-inflammatory and healing benefits for individualized treatments. GENERAL OBJECTIVE: The objective of this study is to investigate the effectiveness of natural active ingredients in cosmetics such as skincare, exploring their benefits beyond aesthetics. METHODOLOGY: This study presents an integrative bibliographic review on skincare and natural products, analyzing articles from 2020 to 2024 in databases such as BVS, PubMed, Google Scholar and Web of Science. Five relevant articles were selected to develop a review framework, focusing on the potential of cosmetics with natural products in adjuvant treatments in skincare. RESULTS: This study reviewed cosmetic formulations with natural products, focusing on their pharmacodynamic and pharmacokinetic properties to enhance aesthetic and therapeutic benefits, especially in combating skin aging and treating acne. six articles were analyzed that highlighted active ingredients such as Aloe Vera and cocoa extract, proving their antioxidant, anti-inflammatory and healing effects. CONCLUSION: The conclusion highlights that a skin care routine with natural cosmetics, such as Centella Asiatica and Aloe Vera, can prevent premature aging and treat conditions such as acnes, due to their anti-inflammatory and antioxidant properties.

Sedation - analgesia - muscle relaxant - withdrawal and delirium practices in pediatric intensive care units in Türkiye

Background. Pain and sedation management is an integral part of pediatric intensive care practice. Sedoanalgesia management must be balanced in order to optimize comfort and avoid complications. In order to achieve this balance, sedoanalgesia management needs to be clarified in pediatric intensive care units (PICU). With this study, we aimed to investigate sedation, analgesia, withdrawal and delirium practices, pharmacologic agent preferences, and current experiences and practices in scoring systems in PICUs in Türkiye. Method. A questionnaire consisting of 57 questions was sent via e-mail to the ‘Pediatric Intensive Care and Emergency’ group, which includes all intensive care specialists, subspecialty students and lecturers in Türkiye. Results. Our study involved 36 pediatric intensive care physicians working in PICUs in Türkiye. Among the PICU specialists who participated in the study, 83.3% stated that they performed routine assessments of sedation efficacy. While dexmedetomidine was the most commonly used sedative agent in patients undergoing noninvasive mechanical ventilation, benzodiazepines were the most preferred pharmacologic agent for sedation during mechanical ventilation. Of the pediatric intensivists who participated in the study, 94.4% stated that they performed routine pain assessments in their units. Of the PICU specialists who participated in the study, 69.4% stated that muscle relaxants were most commonly used to prevent patient-ventilator incompatibility during mechanical ventilation. Of the participants, 88.8% made withdrawal assessments when discontinuing sedo-analgesic agents. Delirium assessment was routinely performed by 58.3% of the participants. Conclusions. This study showed that the practices in sedoanalgesia management in PICUs in Türkiye are in parallel with recommendations of the sedation guideline. Despite the increased sensitivity in sedoanalgesia management, awareness in the management of delirium and withdrawal syndrome is not at the desired level. Therefore, there is a need to develop guidelines, raise awareness and increase training on these issues in our Türkiye.

Pathology of doxorubicin-induced organopathies under different intravenous nicotinamide riboside administration modes

Doxorubicin (DOX) is a potent chemotherapeutic drug, but its clinical use is hindered by significant side effects on vital organs like the heart, kidneys, lungs, liver, and intestines. Currently, there is a lack of effective drugs that can provide simultaneous cardioprotection and organ protection during chemotherapy. Nicotinamide riboside (NR) holds promise as a pharmacological agent capable of offering comprehensive protection against the systemic toxicity caused by DOX. This study aimed to comprehensively evaluate the morphological characteristics of vital organs (heart, lungs, liver, kidneys) in Wistar rats with chronic doxorubicin-induced cardiomyopathy using various intravenous administration modes of NR as a protective agent. Sixty male SPF Wistar rats weighing 283 ± 22 g were divided into four groups: intact, control (DOX administered intraperitoneally), combined mode (the simultaneous use of DOX and NR) and preventive mode (the preliminary use of NR to realize the cumulative effect in cells, and its further joint use together with DOX) intravenous NR administration. Animal observation spanned two months after drug administration, followed by the collection of hearts, lungs, liver, and kidneys for morphological analysis. Echocardiographic assessment confirmed DOX cardiotoxicity. The study revealed that the hearts, kidneys and lungs exhibited more pronounced toxic effects of DOX compared to the liver. Both NR administration modes demonstrated protective effects, with the preventive regime showing the greatest efficacy in safeguarding vital organs.

The role and mechanism of “eight famous herbals in Zhejiang” in cancer via network pharmacology and experimental validation

In recent years, some components and active ingredients from the herbal formula “eight famous herbals in Zhejiang” (Zhe-Ba-Wei) have been reported to possess antitumor properties. However, there is still no systemic study on the role and mechanism of Zhe-Ba-Wei in cancer. To systematically investigate the anticancer efficacy of Zhe-Ba-Wei, we first identified 16 reported active ingredients with gene targets associated with various types of tumors. Second, we screened these active ingredients and their responding multiple shared targets by analyzing the convergence of diverse and tumor-specific target sites and identified four crucial active ingredients (ferulic acid, quercetin, rutin, luteolin), which were characterized by 27 overlapping gene targets. Third, these 27 gene targets were subsequently mapped onto the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology term, and among the 27 total potential targets, 12 were involved in plasma membrane function. Fourth, we investigated the binding affinities between the four crucial active ingredients and their potential targets such as EGFR and MET, both of which are well-known oncogenes in various cancers. Subsequently, an investigation of the computational ADMET properties showed that most of these four ingredients exhibited good ADMET properties. Finally, we found that three active ingredients (ferulic acid, luteolin, and quercetin) could inhibit the proliferation of NSCLC cells and decrease the protein expression of EGFR in a concentration-dependent manner. All these results shed light on the bioactive components, pharmacological effects, and drug development and utilization of Zhe-Ba-Wei, aiming to provide useful support for its further research and clinical application.

Integration of high-resolution mass spectrometry technology with molecular network analysis and systems biology techniques to elucidate the active ingredients and mechanisms of Shiduqing capsules.

Shiduqing Capsules, a well-known Chinese patent medicine, are widely used clinically for the treatment of pruritus. However, to date, there is a lack of research on its pharmacological substances and mechanisms of action. In the current study, the chemical components of Shiduqing Capsules were identified using UHPLC-QE-Orbitrap-MS technology. Molecular network analysis was employed to identify structurally similar compounds to the known chemical components. The potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. The identified targets were further analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the DAVID database. Molecular docking was used to validate the network pharmacology results. Ultimately, A total of 51 chemical components of Shiduqing Capsules were identified. Molecular network analysis identified 21 flavonoids and 13 terpenoids. The core targets of these ingredients include TP53, AKT1, and STAT3. GO and KEGG enrichment analysis revealed 1,371 different biological functions and 177 signaling pathways. Molecular docking confirmed the high affinity between multiple core active ingredients of Shiduqing Capsules and pruritus targets. In conclusion, the effective ingredients of Shiduqing Capsules exert a multifaceted therapeutic effect on pruritus through multiple targets and pathways.

Therapeutic deep eutectic solvent with saponin, optimized through response surface methodology, exert potent in vivo antimicrobial effects against Pseudomonas aeruginosa.

Therapeutic deep eutectic solvents (THEDES) are a type of deep eutectics that can be used as active pharmaceutical ingredients (APIs) by enhancing the drug bioavailability, by increasing the solubility of APIs in aqueous solutions or by increasing their permeability through biological barriers. In this study, we demonstrate the utility of designer THEDES, based on Quillaja Saponin (SAP), a triterpene natural product to unravel the antimicrobial potential of such THEDES. THEDES were prepared by gently mixing and heating five different α- hydroxy acids- malic, citric, tartaric, glycolic, lactic acids and SAP with water as a third component in the THEDES. The antimicrobial assays were performed with the as-prepared SAP-THEDES and among the panel of bacterial strains, saponin-malic acid THEDES [SMA-THEDES] displayed potent activity in disassembling PA biofilms, demonstrating that the SMA-THEDES can serve as therapeutic antibacterial biomaterials. To further optimize, a Box-Behnken- response surface methodology (RSM) experimental design was done and at the optimum conditions of SAP (1.014m.mol), Malic acid (1.003m.mol), Water (0.117m.mol), SMA-THEDES exhibited maximum MIC of P. aeruginosa with the minimum absorbance at 590nm of 0.105. The effectiveness of SMA-THEDES as antibiofilm agents on P. aeruginosa with the mechanism studies have been explored. The colony count from the in vivo infection zebrafish model in the treatment group showed a decline of > 2 fold for SMA-THEDES. Toxicity studies did not reveal any abnormality in liver and brain enzyme levels. Liver morphology images show no severe cytological alterations when treated with SMA-THEDES and were almost similar to the normal liver.

Development and Validation of a Stability Indicating Analytical Method for the Estimation of Gliclazide and Sitagliptin in Bulk Drugs and Tablet Dosage Forms by RP-UPLC: An Application of the Quality-by-Design Approach

Sitagliptin and gliclazide are the active ingredients in OpdualagTM. A highly selective DPP-4 inhibitor, sitagliptin is thought to work in type 2 diabetics by delaying the inactivation of incretin hormones, which increases their concentration and lengthens their duration of effect. Sulfonyl urea mostly enhances insulin secretion from pancreatic β-cells by inhibiting ATP-sensitive K+ channels, leading to depolarisation and Ca2+ influx. Reduced serum glucagon levels and enhanced insulin binding to receptors and target tissues are the mechanisms by which it exerts its effects. Objective: This study aims to create and evaluate an RP-UPLC technique for the detection of sitagliptin and gliclazide in pharmaceutical products by applying AQbD principles. Method: Findings By utilising the Design-expert® programme, we were able to execute a central composite design (CCD) consisting of three components arranged in five distinct layers, which greatly improved the chromatographic conditions. One method that oversees the whole analytical procedure life cycle—from method design and optimisation to validation and continual improvement—is Analytical Quality by Design (AQbD). Results: The retention times for sitagliptin were 1.269 minutes and for gliclazide they were 1.572 minutes. The limits of detection (LOD) and quantitation (LOQ) for Sitagliptin and Gliclazide were 0.19 µg/mL, 0.56 µg/mL, 0.28 µg/mL, and 0.86 µg/mL respectively. The recovery percentages for sitagliptin and gliclazide were found to be 99.15% to 100.54% and 99.93% to 100.58%, respectively. Both drugs were found to be susceptible to oxidative and photolytic breakdown in the forced degradation studies. Conclusions A novel RP-UPLC method has been developed for the quantitative detection of sitagliptin and gliclazide in pharmaceutical formulations, utilising the AQbD-based methodology. This approach is straightforward, rapid, precise, particular, and stable-indicating.

Herbal Drug Use to Treat Urolithiasis: An Updated Review

World Health Organization (WHO) estimates that 12% of the world's population suffers from urolithiasis, a disorder that causes stones to develop in the kidney, bladder, and/or urethra (the urinary system). The illness increases the likelihood of developing chronic renal illnesses in addition to impairing kidney function. Three phases make up the mechanism for the production of stones: nucleation, growth, and aggregation of crystals. Because of their medicinal and antioxidant properties, as well as their active substances, medicinal plants have positive benefits on human health. The traditional medicinal herbs' diuretic qualities are increasingly being backed by scientific research. Urinary calculi patients complain of hematuria, discomfort, or infection. Individuals with tiny, non-obstructing stones or staghorn calculi have moderate, easily managed symptoms in addition to other symptoms. The illness increases the likelihood of developing chronic renal illnesses in addition to impairing kidney function. Therefore, a plant's or a herbal formulation's antiurolithiatic effect may be the result of a combination of its antioxidant, diuretic, and crystallization-inhibiting properties. Keywords: Urolithiasis, diuresis, herbal drug, calcium oxalate stone

Traditional Plants Based Treatment for Kidney Stones: Insight into Herbal Drugs

The deposition of hard crystals created by mineral or salt buildup in the urine canal leads to kidney stones, a frequent urinary tract issue. Urine flow obstruction and excruciating discomfort can be caused by kidney stones. Numerous processes can lead to oxidative stress, which raises the probability of kidney stones developing. The inflammatory response that results from kidney stones forming exacerbates oxidative stress further, creating a vicious cycle. This urological condition, which affects both male and female populations, is becoming more widespread worldwide. Planning the volume of urine produced is a crucial stage in the elimination of kidney stones. Surgery such as shock wave lithotripsy (SWL) and ureteroscopy (URS) is used to treat conditions when the stone has ceased passing through and is causing excruciating discomfort. Because of their medicinal and antioxidant properties, as well as their active substances, medicinal plants have positive benefits on human health. Regrettably, end-stage renal disease is frequently the consequence of side effects brought on the traditional medications used to treat nephrolithiasis. Kidney stones can be avoided by controlling nutrition intake, medication usage, and diet. Agents that are urolithotriptic are medicinal herbs. Examining the natural plants that are utilized to treat the illness is the goal of this review. Finding natural plants that can be used to cure kidney stones was made easier by this review. Keywords: Kidney stones, Urolithiasis, diuresis, herbal drug, calcium oxalate stone

Dendrobium nobile Lindl. alkaloids protect CCl4-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux.

Dendrobium nobile Lindl. alkaloids (DNLA) are considered important active ingredients of Dendrobium, which have a variety of pharmacological functions. Recent studies indicate that DNLA has beneficial activity in acute liver injury. However, the specific mechanism by which DNLA produces liver protective effects is stills unclear. This study was designed to determine whether regulation of autophagy is involved in the mode of action of DNLA in liver protection. Using CCl4-induced acute liver injury (ALI) and cell culture models, the molecular mechanism of DNLA-mediated autophagy regulation was studied. The results showed that DNLA significantly improved CCl4-induced liver damage and oxidative stress, which was confirmed in AML-12 cells. DNLA promoted autophagy in cells treated with CCl4, manifested by reduced protein expressions of p62 and LC3-II. Fluorescence imaging showed a decrease in the number of autophagosomes in AML-12 cells transfected with mCherry-GFP-LC3B. In addition, DNLA inhibited lysosomal membrane permeabilization by upregulating lysosomal associated membrane protein-1 (LAMP1), thereby promoting autophagy, preventing CCl4-induced mitochondrial dysfunction, and reducing the production of mitochondrial reactive oxygen species (ROS). While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl4 induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage.

Correlation between environmental DEET exposure and the mortality rate of cancer survivors: a large-sample cross-sectional investigation.

N, N-Diethyl-meta-toluamide (DEET) is the predominant active ingredient found in insect repellents utilized by consumers. Exposure to DEET has been associated with notable risks to human health. Nonetheless, there is a scarcity of extensive cohort studies investigating the precise correlation between DEET exposure and mortality rates among cancer survivors. The objective of this study is to thoroughly evaluate the connection between DEET exposure and mortality rates in cancer survivors. This study employed individual samples obtained from the National Health and Nutrition Examination Survey (NHANES). Utilizing data from NHANES spanning 2007 to 2016, this study incorporated a cohort of 5,859 cancer survivors for subsequent analysis, following the exclusion of incomplete datasets. Through subgroup analysis, the research examined the impact of quartile levels of 3-diethyl-carbamoyl benzoic acid (DCBA), the primary metabolite of DEET, on cancer survivors across various subgroups within the broader population. Furthermore, the research utilized a multivariable Cox proportional hazards regression model and Kaplan-Meier (KM) curves to investigate the relationship between 3-diethyl-carbamoyl benzoic acid (DCBA), a principal metabolite of DEET, and mortality rates in individuals who have survived cancer. The study identified an association between specific quartiles of DCBA concentration and a decreased risk of all-cause mortality among cancer survivors, specifically in the second (Q2: 0.665-1.95) and third quartiles (Q3: 1.95-6.845). Furthermore, a significant correlation was observed between the third quartile and cancer-specific mortality (Q3: 1.95-6.845), as well as between the second quartile and non-cancer mortality (Q2: 0.665-1.95). The quartiles of DCBA concentration exhibit a statistically significant correlation with total deaths (P < 0.001), cancer-specific deaths (P = 0.009), and non-cancer deaths (P < 0.001) among cancer survivors. The correlation between DCBA and reduced mortality risk in cancer survivors is particularly notable among females and individuals of non-Hispanic Black descent. The detection of DCBA in the urine of adult cancer survivors is strongly associated with increased mortality risks, particularly among females and non-Hispanic Black individuals, warranting further investigation and targeted interventions.

Quantitative Trait Locus Mapping and Candidate Gene Analysis of the Contents of Three Tanshinone Components in Salvia miltiorrhiza Bunge.

Tanshinones are abietane diterpenoid quinone compounds with diverse biological activities and pharmacological effects found in Salvia miltiorrhiza. Leveraging the high-density genetic map established through our prior research endeavors, we conducted a quantitative trait locus (QTL) analysis pertaining to the concentrations of three major tanshinone components, cryptotanshinone, tanshinone I, and tanshinone IIA, in S. miltiorrhiza. This extensive investigation was conducted across three distinct planting environments, ultimately identifying a comprehensive repertoire of 27 discernible QTLs. These QTLs were mapped onto four distinct linkage groups (LG), namely LG1, LG5, LG6, and LG7, which explained 3.11%-37.85% phenotypic variation. Candidate genes were projected based on consistent QTLs detected for each active ingredient in three environments. Nineteen putative candidate genes involved in the regulation of tanshinone biosynthesis were identified. These genes participate in primary metabolic and multiple branching terpenoid biosynthesis pathways, forming a complex regulatory network. Our findings have the potential to offer novel insights into advancing the understanding of the regulatory mechanisms governing tanshinone biosynthesis. Furthermore, these results establish crucial groundwork for gene discovery, marker-assisted selection breeding, and map-based cloning of functional genes associated with tanshinone content in S. miltiorrhiza.