A Comprehensive Review on Pharmacologically Active Phyto-Constituents from Hedychium species.

In this review, we describe and discuss the phytoconstituents present in Hedychium species and emphasize their potential as drug candidates. Though they are widely validated in vitro and in vivo models, to date, no efforts have been made to compile in a single review all the pharmacologically active phytoconstituents from Hedychium species, and their pharmacological and toxicity profile. In this study, we present a reinvestigation of the chemical constituents present in Hedychium species obtained from the essential oil and solvent extraction of the flowers, leaves and rhizomes under consideration. Key databases such as PubMed, Science Direct, Scopus, and Google Scholar amongst others were probed for a systematic search using keywords to retrieve relevant publications on this plant. An exhaustive electronic survey of the related literature on Hedychium species resulted in around 200 articles. Articles published between the years 1975-2021 were included. The studies conducted on either crude extracts, solvent fractions or isolated pure compounds from Hedychium species reported with a varied range of biological effects such as anti-inflammatory, analgesic, antidiabetic, potentially anti-asthmatic, and cytotoxic, among other related activities of the chemical constituents present in its essential oil and solvent extract deployed in this review. Traditional and herbal medication around the world that uses different parts of Hedychium species were considered for anti-inflammatory, skincare, analgesic, anti-asthmatic, anti-diabetic, antidotal uses, among others. These uses support the idea that chemical constituents obtained from solvent extraction may also exert the same action individually or in a synergistic manner. The review concluded that there is scope for computation and biological study to find out possible new targets for strengthening the potency and selectivity of the relevant compounds, and to find a commercial method for extraction of active pharmaceutical ingredients.

Green Synthesis of Titanium Dioxide Nanoparticles Using Ocimum sanctum Leaf Extract: In Vitro Characterization and Its Healing Efficacy in Diabetic Wounds.

Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.

Publics' Perceptions of Community Pharmacists and Satisfaction with Pharmacy Services in Al-Madinah City, Saudi Arabia: A Cross Sectional Study.

Background and Objectives: Pharmacists play a major role in serving patients and delivering pharmaceutical services to the community. It is unclear whether the public fully appreciates what pharmacists can do as key health care providers. This study aims to examine public perceptions of community pharmacists and levels of satisfaction with pharmacy services. Materials and Methods: A cross-sectional study was conducted on a randomly selected sample population (n = 1000) in Saudi Arabia over a period of six months from January through June 2019. A 40-item, structured, self-administered questionnaire was used, comprised of questions on the demographics characteristics of the respondents and their satisfaction with pharmacy services. Descriptive statistics were used to analyze the data. Results: The response rate of the survey was 76.92%. Public opinions were influenced by pharmacists' availability and knowledge, service promptness, and counseling services. Overall, 80.5% of respondents agreed that community pharmacists treat them with respect. Doctors were identified as the preferred source of drug therapy consultation by 58.7% and pharmacists by 41.29%. About 72.8% of respondents agreed that pharmacists provided them with clear instructions about medication use, and 70.2% trusted pharmacists' opinions about medications. About 62.5% of respondents expressed satisfaction with pharmacists, and 64.8% with pharmacy services. Conclusions: Customers' opinions were influenced by pharmacists' availability and knowledge, pharmacy service promptness, pharmacy location, waiting area, medication knowledge, and counseling. However, the public was greatly satisfied with community pharmacists' professionalism and pharmaceutical services. This positive perception provides an opportunity for pharmacists to extend their roles as healthcare professionals.

Enhanced antinociceptive activity of Nigella sativa oil after its combined treatment with honey in rats.

Antinociceptive activity of honey and Nigella sativa (N. sativa) oil are well known. Therefore, aim of this study was to investigate the antinociceptive effect of N. sativa oil and its concurrent administration with honey in rats. The tested animals were randomized into 5 groups: Group (1) Normal saline (0.2ml, p.o.); Group (2) N. sativa oil (1gm/kg, p.o.); Group (3) honey (1gm/kg, p.o.); Group (4) N. sativa oil (1gm/kg, p.o.) + honey (1gm/kg, p.o.): Group (5) pethidine (20mg/kg, S.C.) as positive standard. The antinociceptive activity was tested using radiant heat and tail immersion tests. Antioxidant potential was determined by using in-vitro antioxidant assays. Our findings showed that N. sativa oil and honey have antinociceptive effect, the antinociceptive effect appeared after 30 and 60min of administration and declined after 120 and 180 min. Combined administration of N. sativa oil with Honey increased the antinociceptive effect by 20 to 30% in all models. In addition, the antinociceptive effect of the combination reduced the time for onset of action as well as prolonged its duration of action. In conclusion, combined treatment of N. sativa oil with honey increased its antinociceptive activity, showed faster onset of action and prolonged its duration, the fact that can be utilized in the management of painful conditions in humans.

Thymoquinone Loaded Topical Nanoemulgel for Wound Healing: Formulation Design and In-Vivo Evaluation.

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to <100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

Hepatoprotective effect of rebamipide against methotrexate-induced hepatic intoxication: role of Nrf2/GSK-3ß, NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2 signaling pathways.

OBJECTIVES: The fact that methotrexate (MTX) is hepatotoxic is an important reason to limit its clinical use. Rebamipide (REB) has antioxidant and anti-inflammatory properties and is useful for the treatment of gastro-duodenal ulcers. This study investigated the impact and protective mechanisms of REB against MTX-induced hepatotoxicity in rats. MATERIALS AND METHODS: Animals were divided into four groups of six rats each: a control group, REB group (REB 100 mg/kg/day, orally), MTX control group (20 mg/kg, single i.p.), and MTX + REB group. RESULTS: The administration of MTX induced marked hepatic injury in the form of hepatocyte inflammatory swelling, degeneration, apoptosis, and focal necrosis. In parallel, our biochemical investigations revealed a marked hepatic dysfunction associated with the disturbance of the oxidant/antioxidant balance in the group treated with only MTX. Moreover, MTX led to the down-regulation of the hepatic Nrf2 and Bcl-2 expressions along with a marked elevation in the hepatic NF-κß-p65, GSK-3ß, JAK1, STAT3, PUMA, and Bax expressions. On the other hand, co-treatment with REB significantly ameliorated the aforementioned histopathological, biochemical, and molecular defects caused by MTX treatment. CONCLUSION: the outcomes of the present study showed REB's ability to protect from hepatic injury induced by MTX, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These effects could be attributed to REB's ability to modulate, at least in part, the Nrf2/GSK-3ß,NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2signaling pathways.

Knowledge and awareness of adverse drug reactions and pharmacovigilance practices among healthcare professionals in Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia.

Adverse Drug Reactions (ADRs) are scantly reported with poor contribution by healthcare professionals worldwide and in particular in developing countries. The aim of this study was to assess the knowledge and awareness of adverse drug reactions (ADRs) reporting and pharmacovigilance system among healthcare professionals in Al-Madinah Al-Munawwarah hospitals, Kingdom of Saudi Arabia. A questionnaire was designed addressing; awareness of ADRs, knowledge of pharmacovigilance system, availability of ADRs reporting system, patient counseling about ADRs and documentation of ADRs. The questionnaire was distributed to randomly selected healthcare professionals (n = 585) such as physicians, pharmacists, nurses and pharmacists' technicians of hospitals. Completed questionnaires were collected and data were analyzed. Data were expressed in number as well as percentage. Of the 585 questionnaires circulated, a total of 384 healthcare professionals responded. Healthcare professional categories involved in the study were 148 physicians, 37 pharmacists, 158 nurses and 41 pharmacist technicians. The percent of the respondents who accepted to enroll in the study was 65.64%. Most of the respondents were unable to correctly define the pharmacovigilance term, but they were aware of ADRs. The awareness among healthcare professionals of the national pharmacovigilance system was 39.6%. Pharmacists had a good knowledge of pharmacovigilance and ADRs terminology and showed a more positive attitude to report ADRs. A greater number of the healthcare professionals were aware of ADRs reporting, but practically it is not implemented in hospitals. Most hospitals had follow-up documentation systems, but did not include ADRs reporting. There was no distinct pharmacovigilance system in place. Our study has demonstrated a lack of knowledge and awareness of pharmacovigilance and ADRs reporting among healthcare professionals in hospitals. The poor knowledge of ADRs reporting emphasized the urgent need to implement the appropriate strategies to improve the awareness of pharmacovigilance practices and ADRs reporting in Al-Madinah Al-Munawwarah hospitals.

Long-term moderate dose exogenous erythropoietin treatment protects from intermittent hypoxia-induced spatial learning deficits and hippocampal oxidative stress in young rats.

Exposure to intermittent hypoxia (IH) is associated with cognitive impairments and oxidative stress in brain regions involved in learning and memory. In earlier studies, erythropoietin (EPO) showed a neuroprotective effect in large doses. The aim of the present study was to explore the effect of smaller doses of EPO, such as those used in the treatment of anemia, on IH-induced cognitive deficits and hippocampal oxidative stress in young rats. The effect of concurrent EPO treatment (500 and 1,000 IU/kg/day ip) on spatial learning and memory deficits induced by long-term exposure to IH for 6 weeks was tested using the Morris water maze (MWM) test and the elevated plus maze (EPM) test. Moreover, the effect on hippocampal glutamate and oxidative stress were assessed. Exposure to IH induced a significant impairment of spatial learning and cognition of animals in both MWM and EPM performance parameters. Moreover, hippocampal glutamate and thiobarbituric acid reactive substances (TBARS) increased while antioxidant defenses (GSH and GSH-Px) decreased. EPO in the tested doses significantly reduced the IH-induced spatial learning deficits in both MWM and EPM tests and dose-dependently antagonized the effects of IH on hippocampal glutamate, TBARS, GSH levels, and GSH-Px activity. Treatment with EPO in moderate doses that used for anemia, concurrently with IH exposure can antagonize IH-induced spatial learning deficits and protect hippocampal neurons from IH-induced lipid peroxidation and oxidative stress-induced damage in young rats, possibly through multiple mechanisms involving a potential antioxidative effect.

Dapagliflozin alleviates arsenic trioxide-induced hepatic injury in rats via modulating PI3K/AkT/mTOR, STAT3/SOCS3/p53/MDM2 signaling pathways and miRNA-21, miRNA-122 expression.

Dapagliflozin (DPG) is a sodium-glucose co-transporter 2 inhibitor that is commonly used in the treatment of type 2 diabetes. However, studies have shown that DPG has a protective effect under a variety of experimental conditions through its antioxidative and anti-inflammatory properties. DPG's effect on experimental hepatotoxicity caused by arsenic trioxide (ATO) has yet to be investigated. The purpose of this study was to investigate the protective effect of DPG in preventing hepatic damage caused by ATO and discover the underlying mechanisms. The effect of DPG (1 mg/kg, orally) on ATO (5 mg/kg, i.p.)-induced hepatic injury was evaluated in rats. Serum liver function parameters, as well as oxidative stress biomarkers and inflammatory cytokine levels were assessed. Histopathological changes in the liver were detected using H&E staining. Using Western blotting and PCR techniques, the molecular mechanisms of DPG in ameliorating hepatic injury were investigated. DPG improved liver function by inhibiting histopathological changes, decreasing levels of hepatic function and toxicity parameters measured in both serum and tissues, and exhibiting antioxidant and anti-inflammatory effects, according to the findings. Consistent with the PCR results, DPG also decreased the expression of LC3-II, micro-RNA-122, and micro-RNA-21 while increased the expression of SOCS3. Furthermore, according to western blotting results, DPG was able to reduce the protein expression of AKT, mTOR, PI3K, and STAT3. Although further clinical research is necessary, this study highlights the potential of DPG in preventing liver damage in a rat model of hepatotoxicity induced by ATO.

Nicorandil mitigates arsenic trioxide-induced lung injury via modulating vital signalling pathways SIRT1/PGC-1α/TFAM, JAK1/STAT3, and miRNA-132 expression.

BACKGROUND AND PURPOSE: Nicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as a promising therapeutic approach to treat drug-induced lung toxicity. This study aimed to explore the protective role of nicorandil in arsenic trioxide (ATO)-induced lung injury and to elucidate the underlying mechanistic pathways. EXPERIMENTAL APPROACH: We assessed the effects of nicorandil (15 mg·kg-1, p.o.) in a rat model of pulmonary injury induced by ATO (5 mg·kg-1, i.p.). The assessment included oxidative stress biomarkers, inflammatory cytokine levels, and other biomarkers, including sirtuin-1, sirtuin-3, STAT3, TFAM, and JAK in lung tissue. Histological examination using H&E staining and molecular investigations using western blotting and PCR techniques were conducted. KEY RESULTS: In our model of lung injury, treatment with nicorandil ameliorated pathological changes as seen with H&E staining, reduced tissue levels of toxicity markers, and exerted significant antioxidant and anti-inflammatory actions. On a molecular level, treatment with nicorandil down-regulated JAK, STAT3, PPARγ, Nrf2, VEGF, p53, and micro-RNA 132 while up-regulating Sirt1, 3, TFAM, AMPK, and ERR-α in lung tissue. CONCLUSIONS AND IMPLICATIONS: The results presented here show nicorandil as a significant agent in attenuating lung injury induced by ATO in a rodent model. Nonetheless, further clinical studies are warranted to strengthen these findings.

Chitosan-based topical formulation integrated with green-synthesized silver nanoparticles utilizing Camellia sinensis leaf extracts: A promising approach for managing infected wounds.

This study explores the eco-friendly biosynthesis of silver nanoparticles (AgNPs) utilizing Camellia sinensis leaf extract. We assess their antioxidant and antibacterial properties. Furthermore, we impregnated AgNPs into 2 % chitosan (CHS) gel and assessed their wound-healing potential in Escherichia coli and Staphylococcus aureus infected wounds. Optimized AgNPs demonstrated a mean particle size of 36.90 ± 1.22 nm and a PDI of 0.049 ± 0.001. Green-synthesized AgNPs exhibited enhanced free radical inhibition (IC50: 31.45 µg/mL, 34.01 µg/mL, 27.40 µg/mL) compared to leaf extract (IC50: 52.67 µg/mL, 59.64 µg/mL, 97.50 µg/mL) in DPPH, hydrogen peroxide, and nitric oxide free radical scavenging assays, respectively. The MIC/MBC values of AgNPs against E. coli and S. aureus were 5 ppm/ 7.5 ppm and 10 ppm/ 15 ppm, respectively. Furthermore, our study showed that green-synthesized AgNPs at MIC significantly reduced the biofilm production of E. coli (70.37 %) and S. aureus (67.40 %). The CHS/AgNPs gel exhibited potent wound healing activities, comparable to a commercial cream with the re-epithelialization period of 8.16 ± 0.75. Histological analysis demonstrated enhanced skin regeneration with a thicker epidermal layer, well-defined papillary dermal structure, and organized collagen fibers. In summary, these findings hold promise for addressing bacterial infections, particularly those associated with biofilms-related wound infections.

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy.

Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV-Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti-O-Ti bond is identified by observing a peak between 400 and 800 cm-1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 µg/mL and standard (Vitamin C) IC50 is 87.62 µg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.

Reno-protective effect of nicorandil and pentoxifylline against potassium dichromate-induced acute renal injury via modulation p38MAPK/Nrf2/HO-1 and Notch1/TLR4/NF-κB signaling pathways.

BACKGROUND: Occupational and environmental exposure to chromium compounds such as potassium dichromate (PDC) (K2Cr2O7) has emerged as a potential aetiologic cause for renal disease through apoptotic, and inflammatory reactions. The known potent antioxidants such as nicorandil (NIC) and/or pentoxifylline (PTX) were studied for their possible nephroprotective effect in PDC-treated rats. METHODS: Forty male Wistar rats were divided into five groups; control, PDC group, NIC+PDC, PTX+PDC group, and combination+PDC group. Nephrotoxicity was evaluated histopathologically and biochemically. Invasive blood pressure, renal function parameters urea, creatinine, uric acid and albumin, glomerular filtration rate markers Cys-C, Kim-1 and NGAL, inflammatory markers IL-1ß, IL-6, TNF-α, TGF-ß, COX-II, p38MAPK, NF-κB and TLR4, oxidative stress SOD, GSH, MDA, MPO, HO-1 and Nrf2 and apoptotic mediators Notch1 and PCNA were evaluated. Besides, renal cortical histopathology was assayed as well. RESULTS: PDC led to a considerable increase in indicators for kidney injury, renal function parameters, invasive blood pressure, oxidative stress, and inflammatory markers. They were markedly reduced by coadministration of PDC with either/or NIC and PTX. The NIC and PTX combination regimen showed a more significant improvement than either medication used alone. Our results demonstrated the nephroprotective effect of NIC, PTX, and their combined regimen on PDC-induced kidney injury through suppression of oxidative stress, apoptosis, and inflammatory response. CONCLUSION: Renal recovery from PDC injury was achieved through enhanced MAPK/Nrf2/HO-1 and suppressed Notch1/TLR4/NF-κB signaling pathways. This study highlights the role of NIC and PTX as effective interventions to ameliorate nephrotoxicity in patients undergoing PDC toxicity.

Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

Febuxostat alleviates Arsenic Trioxide-Induced renal injury in Rats: Insights on the crosstalk between NLRP3/TLR4, Sirt-1/NF-κB/TGF-ß signaling Pathways, and miR-23b-3p, miR-181a-5b expression.

Febuxostat (FBX), a xanthine oxidase inhibitor, is known to improve renal function and can show promise as a therapeutic agent for preventing drug-induced nephrotoxicity. This study aimed to explore the protective effect of FBX in preventing renal damage caused by arsenic trioxide (ATO) toxicity and uncover the underlying mechanisms. The researchers examined how FBX (10 mg/kg, orally) affected ATO-induced kidney injury (5 mg/kg, intraperitoneally) in rats. Kidney function and toxicity parameters in serum and oxidative stress biomarkers and inflammatory cytokine levels in renal tissue were measured. H&E staining was used to detect histopathological changes in the kidney. Network the molecular mechanisms of FBX in improving kidney injury were investigated using Western blotting and PCR techniques. The findings showed that FBX improved kidney function by inhibiting the pathological changes seen in H&E staining, decreasing levels of probed kidney function and toxicity measures in serum and tissue, and exhibiting antioxidant and anti-inflammatory effects. FBX decreased MDA, MPO, TNF-α, IL-1ß, IL-6, COX-II, and NADPH oxidase levels, while increased GSH, GPx, SOD, and IL-10 levels. FBX also reduced the expression of NLRP3, ASC, TLR4, and micro-RNA 181a-5b while increased the expression of IKBα, Sirt-1, and micro-RNA 23b-3p, according to Western blotting and PCR results. In conclusion, FBX can play a vital role in reducing kidney injury in cases of ATO-induced nephrotoxicity, though more clinical research needs to be conducted.

Alternative Non-Drug Treatment Options of the Most Neglected Parasitic Disease Cutaneous Leishmaniasis: A Narrative Review.

With more than 12 million cases worldwide, leishmaniasis is one of the top 10 neglected tropical diseases. According to the WHO, there are approximately 2 million new cases each year in foci in around 90 countries, of which 1.5 million are cutaneous leishmaniasis (CL). Cutaneous leishmaniasis (CL) is a complex cutaneous condition that is caused by a variety of Leishmania species, including L. (Leishmania) major, L. (L) tropica, L. (L) aethiopica, L. (L) mexicana, L. (Viannia) braziliensis, and L. (L) amazonensis. The disease imposes a significant burden on those who are affected since it typically results in disfiguring scars and extreme social stigma. There are no vaccines or preventive treatments available, and chemotherapeutic medications, including antimonials, amphotericin B, miltefosine, paromomycin, pentamidine, and antifungal medications, have a high price tag, a significant risk of developing drug resistance, and a variety of systemic toxicities. To work around these limitations, researchers are continuously looking for brand-new medications and other forms of therapy. To avoid toxicity with systemic medication use, high cure rates have been observed using local therapy techniques such as cryotherapy, photodynamic therapy, and thermotherapy, in addition to some forms of traditional therapies, including leech and cauterization therapies. These CL therapeutic strategies are emphasized and assessed in this review to help with the process of locating the appropriate species-specific medicines with fewer side effects, lower costs, and elevated cure rates.

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia.

Background: The plant Tinospora cordifolia (TC), traditionally known as guduchi or giloy, is used for a number of health conditions as a nutritional supplement and rejuvenation medicine. Its nutritional supplementary products are traditionally recommended for a wide range of health issues, including diabetes, menstruation discomfort, fever, obesity, inflammation, and more. Unfortunately, there has not been extensive research into its effectiveness in treating or managing insulin resistance, lipid and carbohydrate metabolism, hormonal imbalance, and metabolic syndrome-associated polycystic ovary syndrome (PCOS). Methods: Consequently, the present study was designed to induce insulin resistance, dyslipidemia, hormonal abnormality, hyperglycemia, and menstrual disturbance of PCOS using dehydroepiandrosterone (DHEA) in mice and study the effect of oral TC extracts on these factors by using ancient and modern technologies. During the 21-day study, 6 mg/100 g/day of DHEA was given to female mice. Levels of glucose, insulin, lipids, and hormones were estimated. In addition to being seen with the naked eye, the morphological and microscopic changes were also observed on histology slides. Results: The study outcomes show that pretreatment with TC preparations significantly improved biochemical and histological abnormalities in female mice. Diestrus phase was only observed in DHEA-treated animals, while cornified epithelial cells were present in TC-treated mice. Pretreatment with TC satva showed significant (p < 0.001) reductions in body weight compared to placebo. Fasting blood glucose, 1-h OGTT, and 2-h OGTT levels were all significantly lower in TC satva- and oil-treated animals in comparison to the disease control group (p < 0.001). Treatment with TC extracts resulted in a normalization of estradiol, progesterone, and testosterone levels (p < 0.05). Treatment with TC extract improved lipid profiles (p < 0.001), LH/FSH ratios (p < 0.01), fasting insulin levels (p < 0.001), HOMA-IR (p < 0.001), HOMA-Beta (p < 0.001), and QUICKI (p < 0.001). Both macroscopic and microscopic alterations were seen to be restored after TC extract treatment. After being treated with TC satva, oil, and hydroalcoholic extract, the severity of PCOS decreased by 54.86%. Conclusions: These findings lead us to the conclusion that TC extracts and satva as nutritional supplements are useful for treating PCOS and associated symptoms. It is recommended that additional research be conducted to determine the molecular mechanism of action of TC nutritional supplements on PCOS-related changes in metabolic profiles. We also recommend further clinical studies to explore the clinical efficacy and effectiveness of TC nutritional supplements in treating and/or managing PCOS.

Predictors of antibiotic use in pregnant women attending Najran University Hospital, Saudi Arabia.

OBJECTIVES: To determine the prevalence of antibiotic use by pregnant women in Najran, Saudi Arabia. METHODS: A total of 125 women aged 18 to 45 with a full-term pregnancy participated from October to December 2019. Age, order of current pregnancy, body mass index (BMI), history of miscarriage, and comorbidity were used to estimate antibiotic use. RESULTS: The majority were Saudis (67.2%), aged 30-35 (39.2%) years, with no history of miscarriage (53.6%), second order of pregnancy (26.4%), and going through weeks 20-25 of pregnancy (21.6%). A total of 26.4% of pregnant women had antibiotic prescriptions in the study population. Pregnant women under 30 years were less likely to receive antibiotics. CONCLUSION: The results found an association between maternal age, order of pregnancy and antibiotic use during pregnancy. An association was observed between maternal BMI and the occurrence of adverse drug reactions after antibiotic use. In addition, a history of miscarriage was negatively associated with the use of antibiotics during pregnancy. These predictors of antibiotic administration have the potential to serve as general health indicators and to direct preventative strategies aimed at increasing the rational use of antibiotics.

Antioxidant Properties Mediate Nephroprotective and Hepatoprotective Activity of Essential Oil and Hydro-Alcoholic Extract of the High-Altitude Plant Skimmia anquetilia.

There are many high-altitude plants such as Skimmia anquetilia that are unexplored for their possible medicinal values. The present study was conducted to examine the antioxidant activities of Skimmia anquetilia (SA) using in vitro and in vivo models. The SA hydro-alcoholic extracts were investigated using LC-MS for their chemical constituents. The essential oil and hydro-alcoholic extracts of SA were evaluated for pharmacological properties. The antioxidant properties were evaluated using in vitro DPPH, reducing power, cupric reducing antioxidant power, and metal chelating assays. The anti-hemolytic activity was carried out using a human blood sample. The in vivo antioxidant activities were evaluated using CCL4-induced hepatotoxicity and nephrotoxicity assay. The in vivo evaluation included histopathological examination, tissue biochemical evaluation such as the kidney function test, catalase activity, reduced glutathione activity, and lipid peroxidation estimation. The phytochemical investigation showed that the hydro-alcoholic extract contains multiple important active constituents such as L-carnosine, acacetin, linoleic acid, leucylleucyl tyrosine, esculin sesquihydrate, etc., similar to the components of SA essential oil reported in a previous study. The high amount of total phenolic content (TPC) and total flavonoid content (TFC) reflect (p < 0.001) a high level of reducing power, cupric reducing, and metal chelating properties. This significantly (p < 0.001) inhibited enlargement of the liver, with a significant reduction in ALT (p < 0.01) and AST (p < 0.001). Highly significant improvement in the functioning of the kidney was noted using the blood urea and creatinine (p < 0.001) levels. Tissue-based activities showed a major rise in catalase, reduced glutathione, and reduced lipid peroxidation activities. We conclude from this study that the occurrence of a high quantity of flavonoid and phenolic contents had strong antioxidant properties, leading to hepatoprotective and nephroprotective activity. Further active constituent-specific activities should be evaluated.

New Megastigmane and Polyphenolic Components of Henna Leaves and Their Tumor-Specific Cytotoxicity on Human Oral Squamous Carcinoma Cell Lines.

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves' 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H2O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound (1) along with tannin-related metabolites, benzoic acid (2), benzyl 6'-O-galloyl-ß-D-glucopyranoside (3), and ellagic acid (4), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O-glucosidic ellagitannins, heterophylliin A (5), and gemin D (6), in addition to four known C-glycosidic ellagitannins, lythracin D (7), pedunculagin (8), flosin B (9), and lagerstroemin (10). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D (1H and 13C) and 2D (1H-1H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α]D, and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a ß-ionone, a degradative product of the common metabolite ß-carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 (7) and pedunculagin (8) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders.