The landscape of novel strategies for acute myeloid leukemia treatment: Therapeutic trends, challenges, and future directions.

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge. Therefore, discovery of novel treatment targets, optimization of combination strategies, and development of efficient therapeutics are urgently required. This review provides a detailed and comprehensive discussion on the advantages and limitations of targeted therapies as a single agent or in combination with others. Furthermore, the innovative therapeutic approaches including hyperthermia, monoclonal antibody-based therapy, and CAR-T cell therapy are also introduced, which may provide safe and viable options for the treatment of patients with AML.

Pharmacological and toxicological evaluation of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxoide against haloperidol induced Parkinson like symptoms in animal model: In-vitro and in-vivo studies.

In Parkinson's disease (PD), degradation of dopaminergic neurons in substantia nigra causes striatal deficiency of dopamine, which results in tremors, bradykinesia with instability in posture, rigidity and shuffled gait. Prevalence of PD increases with age as from 65 to 85 years. In an attempt to devise targeted safe therapy, nanoparticles of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (MBD) (MBDN), were prepared and their acute toxicity and safety was evaluated. Thirty-six healthy albino mice were randomly divided into six groups (n = 6): normal control, diseased control, standard (levodopa/carbidopa (100/25 mg/kg) and the remaining three groups were administered 1.25, 2.5 and 5 mg/kg MBDN during 21 days study. Except control, all mice, were injected haloperidol (1 mg/ kg i.p.) 1-h prior to treatment to induce PD. Acute toxicity test showed, no effect of MBDN on lipid profile, brain, renal and liver function and histoarchitecture of kidney, liver and heart, except decreased (p < 0.05) platelet count. Behavioral studies showed significant improvement (p < 0.001) in motor function and reduction of oxidation status in a MBDN in a dose dependent manner. Thus, the study findings revealed significance of MBDN as a selective MAO-B inhibitor for the improvement of Parkinson's symptoms in animal model.

Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARα.

The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.

Role of medicinal herbs and phytochemicals in post burn management.

Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.

Involvement of PML-I in reformation of PML nuclear bodies in acute promyelocytic leukemia cells by leptomycin B.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17), resulting in the expression of PML-RARα fusion protein, which disrupts the normal PML nuclear bodies (PML-NBs) to micro-speckled pattern, leading to loss of their original functions. Moreover, reformation of PML-NBs in APL by arsenic is considered as one of the important step for APL treatment. Leptomycin B (LMB), a nuclear export inhibitor, is commonly used to inhibit the proteins exporting from the nucleus to the cytoplasm. In the present study, we found that LMB could induce the reformation of PML-NBs in leukemia NB4 cells as well as in APL blast cells from the patients, implying that nuclear shuttle proteins might be involved in the reformation of PML-NBs. Herein, we further found that LMB totally lost the ability to induce PML-NBs reformation when the endogenous PML gene was knocked out, indicating that endogenous PML protein is probably involved in the reformation of PML-NBs. More interestingly, among all PML isoforms (i.e., seven isoforms), reformation of PML-NBs was only observed when co-transfection of PML-RARα with PML-I after LMB treatment. Similarly, deletion of nuclear export signal (NES) of PML-I could also reform PML-NBs, suggesting that the protein level of endogenous PML-I in nucleus is important for the reformation of PML-NBs that interfered by PML-RARα fusion protein. Additionally, LMB has synergistic effect with iAsIII on enhancing PML-RARα fusion protein degradation, and it might provide new insight into APL treatment at clinical level in the near future.

Phenylarsine Oxide Can Induce Degradation of PLZF-RARα Variant Fusion Protein of Acute Promyelocytic Leukemia.

PLZF-RARα is the second most frequent variant acute promyelocytic leukemia (APL) fusion protein that ranks after PML-RARα in APL. However, PLZF-RARα is resistant to current front line APL treatments including all transretinoic acid (ATRA), arsenic trioxide (ATO), and chemotherapy (i.e., Idarubicin). Herein, we for the first time report that phenylarsine oxide (PAO) could effectively induce PLZF-RARα variant fusion protein degradation through ubiquitin proteasome degradation pathway by apoptosis, which indicates that PAO might be a potential candidate for the treatment of PLZF-RARα variant APL. Given that, this study highlights the potential benefit of arsenic-organometallic compound PAO in APL treatment.

Selection and characterization of novel DNA aptamer against colorectal carcinoma Caco-2 cells.

Aptamers are short, single-stranded nucleic acid (DNA or RNA) oligonucleotides that can be obtained by a technique called systematic evolution of ligands by exponential enrichment (SELEX) in vitro. Due to superior properties such as small size, high binding affinity, and stability, they are considered to be feasible tools for diagnosis and treatment of disease. In the current study, we attempted to screen a high-affinity DNA aptamer to selectively target the colorectal carcinoma Caco-2 cells by using cell-based SELEX approach. After 14 consecutive rounds of selection, aptamer ApC1 was identified. Confocal microscopy results revealed that ApC1 could rapidly internalize into Caco-2 cells but not HEK 293 cells. Moreover, it showed high specificity to Caco-2 cells rather than other cell lines such as 293T, HeLa, MCF-7, HL-60, and NB4. Collectively, our results demonstrated that aptamer ApC1 has high specificity to colorectal carcinoma Caco-2 cells, which could be further applied for targeted therapy of colorectal cancer in future studies.

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes.

Arsenic trioxide (As2O3) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As2O3 resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation. Here, three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners. Interestingly, PAO is found to have potential effect on induction of mutant PML-IV (A216V) protein solubility changes and degradation, but no appreciable effects were found following exposure to high concentrations of iAsIII, dimethylarsinous acid (DMAIII) and adriamycin (doxorubicin), even though they cause cell death. Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.

Analgesic, anti-inflammatory and antipyretic activity of Salvia moorcroftiana.

Salvia moorcroftiana is an herbaceous plant commonly known as "Kallijari" in Pakistan and belongs to the family Lamiaceae. This study was carried out to evaluate its scientific base for its traditional use in pain, fever and inflammation. The powdered plant was extracted by the method of cold maceration using aqueous methanol (70:30) as solvents. Hot plate, flick tail and acetic acid induced writhing test were utilized for analgesic assessment. Anti-inflammatory activity was evaluated by carageenan-induced mice paw edema. Brewer's induced pyrexia was used for the evaluation of antipyretic activity. Non-significant (p<0.01) results as compared to the standard were obtained in all experiments. It was evident from acute toxicity study that plant was non-toxic in nature. It is concluded from the study that plant had the potential to be safely used for pain, fever and inflammation.

Report: Analgesic and anti-inflammatory activity of aqueous-methanolic extract of Aerva javanica.

The present study was aimed to investigate the analgesic and anti-inflammatory activity of aqueous methanolic extract of Aerva javanica. For measuring analgesic activity, writhing test, hot plate method and formalin test were performed and abdominal writhing was induced by intra-peritoneal injection of 0.2ml of 3% acetic acid. While in formalin test, pain was experimentally induced by injecting 25 µl of 2.5% formalin in left hind paw. In hot plate method, pain was induced thermally by keeping the animals on a hot plate with temperature of about 51°C. Anti-inflammatory activity was assessed by carrageen an induced mice paw edema. The results showed that the extract had significant analgesic activity (p<0.05- p<0.001) and anti-inflammatory activity (p<0.01-p<0.001). Therefore, it was concluded from this study that the extracts of Aerva javanica may be used against pain and inflammation.

Report: Antimicrobial activity of Kalanchoe laciniata.

This study was conducted to identify antimicrobial potential of Kalanchoe laciniata. The plants were extracted with 30-70% aqueous-methanol and n-hexane. The antimicrobial activities were examined using agar well diffusion method against bacteria (Staphylococcus aureus, Escherichia coli) and fungi (Candidaalbicans). Results showed that E. coli were more sensitive than Staphylococcus aureus and Candida albicans. The largest zone of inhibition (52 mm) was recorded against E. coli with the n-hexane extract of Kalanchoe laciniata.

Formulation development of intermediate release Nimesulide tablets by CCRD for IVIVC studies.

Simple and cost effective study consisting of three steps, comparison of micromeritic properties of different blends i.e. placebo without API and Nimesulide containing, Use of central composite design (CCRD) for intermediate release Nimesulide tablets and stability results of three selected Nimesulide tablet formulations which were calculated by using R Gui. Different concentrations of Avicel, hydroxypropyl methyl cellulose (HPMC) and magnesium stearate were used as variables in central composite design and two types blend i.e., with or without Nimesulide were selected for bulk density, tap density, percentage compressibility; angle of repose and Hausner's ratio. Blending rate constant was performed after applying the different mixing times like 3, 6, 9 and 12 minutes. Twenty intermediate release formulations were designed and three formulations were chosen for compression by direct compression method on the basis of compressibility index. Physicochemical properties and best release pattern in four hours in different dissolution medium were successfully measured. Relative densities, porosity of tablets were compared with tensile strength of tablet and weight variation, hardness, friability and dissolution was performed by simple experiments. Presence of Nimesulide in the bulk increased all micromeratic tests while 9 minutes was best mixing time. The hardness of NM containing tablets increased with the increase of relative density. The release pattern was further analyzed by model dependent i.e. zero order, first order and Higuchi, Korse-meyer and Pappas, Hixson Crowell and model independent kinetic model i.e., f2 value respectively. R Gui explained the F16 formulation shows the best result in stability studies with shelf life 72 months.

Crosslinked PVA-g-poly(AMPS) Nanogels for Enhanced Solubility and Dissolution of Ticagrelor: Synthesis, Characterization, and Toxicity Evaluation.

In this study, we synthesized PVA-g-poly(AMPS) nanogels with the aim of enhancing the solubility and dissolution of ticagrelor (TGR). Ticagrelor, a noncompetitive, reversible P2Y12 receptor antagonist, is prescribed to treat acute coronary syndrome. Ticagrelor has restricted oral bioavailability (≈36%) because of its poor solubility and permeability. The free radical polymerization methodology was employed to synthesize nanogels with varied concentrations of poly(vinyl alcohol) (polymer), 2-acrylamido-2-methylpropanesulfonic acid (monomer), and N,N-methylene bis(acrylamide) (crosslinker). The prepared nanogels were analyzed by swelling studies, % drug entrapment efficiency (DEE), solubility studies, in vitro drug release studies, zeta sizer, Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The optimized formulation (PA5) revealed a particle size of 45.86 nm, with a polydispersity index (PDI) of 0.41 and a %DEE of 85.1%. FTIR spectroscopy, XRD, and SEM confirmed the formation of crosslinked nanogels with amorphous and porous structures, and TGA/DSC proved their thermal stability. In vitro dissolution studies showed 99.91% drug release, and the ticagrelor solubility from the synthesized formulations was significantly improved up to 8.2-fold. All formulations followed the Korsmeyer-Peppas model with the Fickian diffusion as the release mechanism. The toxicity studies carried out on rats and the MTT assay on the Caco-2 cell line validated the biocompatibility of the nanogel formulations. The outcomes of the current study led to the conclusion that the PVA-g-poly(AMPS) nanogels synthesized by us could be used as dedicated pharmaceutical delivery systems to achieve enhanced solubility and dissolution of ticagrelor.

Phytochemicals-based investigation of Rubia cordifolia pharmacological potential against letrozole-induced polycystic ovarian syndrome in female adult rats: In vitro, in vivo and mechanistic approach.

Polycystic Ovarian Syndrome (PCOS) is a metabolic, reproductive, and endocrine disorder affecting women of fertile age. This study aimed to formulate a phytochemicals-based standardized aqueous ethanolic extract of Rubia cordifolia (SERC) to explore its pharmacological potential in PCOS-induced female rats and elucidate its mechanism. HPLC analysis revealed the presence of phytochemicals such as chlorogenic acid, p-coumaric acid, gallic acid, and kaempferol. Thirty female adult rats were divided into two groups for induction of PCOS (5 female rats in the normal control group + 25 female rats in the disease-induced group). PCOS was induced by administering letrozole (1 mg/kg p.o.) for 6 weeks. After PCOS induction, animals of the disease-induced group were divided into five groups: one group used as disease control (PCOS) group, one group on metformin (20 mg/kg), and three groups on SERC (200, 400, and 600 mg/kg). Histopathological analysis showed that PCOS induction reduced corpus luteum and developing follicles and increased cystic follicles. In comparison, SERC treatment improved ovulation with more primary and developing follicles. SERC reduced the serum insulin, LH surge, and testosterone levels while improving the FSH, estrogen, and progesterone serum levels. SERC significantly improved the oxidation status of the liver and normalized the lipid profile and liver function markers. In conclusion, SERC treated PCOS, and the suggested mechanism might be the restoration of aromatase activity and background inflammatory status improvement in ovaries.

Correction to "Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression".

[This corrects the article DOI: 10.1021/acsomega.3c09667.].

Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression.

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats.

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

Curcumin-loaded soluplus® based ternary solid dispersions with enhanced solubility, dissolution and antibacterial, antioxidant, anti-inflammatory activities.

Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 µg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive (Staphylococcus aureus, Bacillus cereus) and gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.

Topical Delivery of Terbinafine HCL Using Nanogels: A New Approach to Superficial Fungal Infection Treatment.

This study investigated pH-responsive Terbinafine HCL (TBH)-loaded nanogels as a new approach to treating superficial fungal infections. Acrylic acid (AA) is a synthetic monomer that was crosslinked with a natural polymer (gelatin) using a free radical polymerization technique to fabricate gelatin-g-poly-(acrylic acid) nanogels. Ammonium persulphate (APS) and N, N'-methylene bisacrylamide (MBA) were used as the initiator and crosslinker, respectively. Developed gelatin-g-poly-(acrylic acid) nanogels were evaluated for the swelling study (pH 1.2, 5, 7.4), DEE, particle size, FTIR, thermal stability (TGA, DSC), XRD, SEM, DEE, and in vitro drug release study to obtain optimized nanogels. Optimized nanogels were incorporated into 1% HPMC gel and then evaluated in comparison with Lamisil cream 1% for TBH stratum corneum retention, skin irritation, and in vitro and in vivo antifungal activity studies. Optimized nanogels (AAG 7) demonstrated a 255 nm particle size, 82.37% DEE, pH-dependent swelling, 92.15% of drug release (pH) 7.4 within 12 h, and a larger zone of inhibition compared to Lamisil cream. HPMC-loaded nanogels significantly improved the TBH skin retention percentage, as revealed by an ex vivo skin retention study, indicating the usefulness of nanogels for topical use. In vivo studies conducted on animal models infected with a fungal infection have further confirmed the effectiveness of nanogels compared with the Lamisil cream. Hence, Gelatin-g-poly-(acrylic acid) nanogels carrying poorly soluble TBH can be a promising approach for treating superficial fungal infections.

Dose Dependent Effects of Aqueous Extract of Garcinia cambogia Desr. Against Letrozole Induced Polycystic Ovarian Syndrome in Female Adult Rats With Possible Mechanisms Exploration.

Background: Polycystic ovarian syndrome (PCOS) is an endocrine metabolic disorder of women. Purpose: This study aimed to explore the potential of aqueous extract of Garcinia cambogia Desr. (AEGC) in PCOS. Methodology: The HPLC was used to determine the phytoconstituents present in Garcinia cambogia. Thirty adult female albino rats were divided into 6 groups: Normal control (NC) disease Control (PCOS; letrozole 1 mg/kg), plant extract (AEGC 100, 300, 500 mg/kg) and standard (metformin; 20 mg/kg). Disease was confirmed by vaginal smear cytology. After 10 weeks, animals were euthanized, ovaries dissected for histopathology, blood collected for hormonal and biochemical analysis. Results: HPLC analysis showed the presence of phenolic contents; chlorogenic acid, gallic acid, coumaric acid while flavonoid contents were quercetin, kaempferol, and rutin. After treatment, there was dose dependent reduction of weight, ovarian cysts, improvement of follicle growth. DPPH radical scavenging percentage was 67.89%. Hormonal analysis showed a significant improvement (P < .05) in follicle stimulating hormone (FSH), estrogen, and progesterone while a reduction in testosterone, luteinizing hormone (LH) and insulin level. Antioxidant enzymatic markers were significantly (P < .05) increased. Lipid profile and LFTs were also improved. Conclusions: The study validated the potential of Garcinia cambogia in the management of PCOS.