Investigating Bacopa monnieri L. Therapeutic Potential for the Treatment of Neurological Diseases.

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (Aß) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects.

Hyperbaric Oxygen Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma: A Prospective Study.

Background Non-union, chronic pain, functional disability, and infection are all things that have been associated with open fractures with severe soft tissue damage leading to the need for additional hospitalization, and sometimes even subsequent surgeries and weeks or months of rehabilitation. Open fractures and severe musculoskeletal injuries are occasionally treated with hyperbaric oxygen therapy (HBOT) in an effort to reduce the risk of complications and increase the likelihood of a successful recovery. Methods A prospective randomized controlled study was done between January 2019 and August 2022 at a tertiary health care center including 60 patients with a severe soft tissue injury (Grade II and III) divided into two groups - group-CT (30 patients who received conventional treatment) and group HT (30 patients, who received HBOT in addition to conventional treatment). The outcome was measured according to the Bates-Jensen Wound Assessment Tool. Results The wound size, depth, and granulation were significantly reduced in group-HT patients. In the final session, the patient's severity of the wound in group-HT was significantly reduced (P = 0.0001) compared to group-CT. Conclusions Patients who received HBOT reported a significant improvement in their wounds.

Isolation and characterization of N-(2-Hydroxyethyl)hexadecanamide from Colletotrichum gloeosporioides with apoptosis-inducing potential in breast cancer cells.

Endophytic fungi are a well-established reservoir of bioactive compounds that are pharmaceutically valuable and therefore, contribute significantly to the biomedical field. The present study aims to identify the bioactive anticancer compound from ethyl acetate extract of fungal endophyte, Colletotrichum gloeosporioides associated with the leaf of the medicinal plant Oroxylum indicum. The fatty acid amide compound N-(2-Hydroxyethyl)hexadecanamide (Palmitoylethanolamide; PEA) was identified using antioxidant activity-guided fractionation assisted with tandem liquid chromatography coupled with quadrupole time of flight mass spectrometry, Fourier transform-infrared spectroscopy, time-of-flight mass spectrometry, and nuclear magnetic resonance. In-Silico molecular docking analysis showed that PEA potentially docked to the active sites of apoptosis-inducing proteins including BAX, BCL-2, P21, and P53. Further validation was done using in vitro study that showed PEA inhibitsthe proliferation, alters nuclear morphology and attenuates the wound closure ability of MDA-MB-231 and MCF-7 cells. PEA induces apoptosis via upregulating cell-cycle arrest (P21), tumor suppression (P53), pro-apoptotic (BAX, CASPASE-8, and FADD) genes, and downregulating anti-apoptotic gene BCL-2. The upregulation of the active form of Caspase-3 was also reported. This is the first-ever report for the isolation of PEA from C. gloeosporioides with anticancer activity against human breast cancer cells and therefore holds great potential for future therapeutics.

Bioprospecting of fungal endophytes from Oroxylum indicum (L.) Kurz with antioxidant and cytotoxic activity.

Oroxylum indicum (L.) Kurz, a medicinal plant, shows numerous pharmacological properties which may be attributed to the bioactive compounds produced by O. indicum or due to associated endophytes. In the present study, leaf of O. indicum was evaluated for the presence of associated fungal endophytes, and antioxidant and cytotoxic activities of bioactive compounds produced from them. Using culture-dependent approach, eight fungal endophytes belonging to five different genera were identified. Two endophytes Daldinia eschscholtzii and Ectophoma multirostrata have been reported for the first time from the leaf of O. indicum plant. High-performance thin-layer chromatography (HPTLC) of ethyl acetate (EA) extract of isolated fungal endophytes showed a distinct fingerprinting profile in EA extract of Colletotrichum gloeosporioides. Among identified endophytes, EA extract of C. gloeosporioides showed significant antioxidant activity against DPPH free radical, superoxide anion radical, nitric oxide radical and hydroxyl radical with EC50 values of 22.24±1.302 µg/mL, 67.46±0.576 µg/mL, 80.10±0.706 µg/mL and 61.55±1.360 µg/mL, respectively. EA extract of C. gloeosporioides exhibited potential cytotoxicity against HCT116, HeLa and HepG2 cancer cell lines with IC50 values of 76.59 µg/mL, 176.20 µg/mL and 1750.70 µg/mL, respectively. A comparative HPTLC fingerprinting and the antioxidant activity of C. gloeosporioides associated with two different hosts (leaf of O. indicum and dead twigs of other plant) showed that C. gloeosporioides produces bioactive compounds in a host-dependent manner.

Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia.

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

Role of natural compounds in preventing and treating breast cancer.

Breast cancer (BrCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women. Alarming increases in the cases quests for more effective treatment of BrCa. As most chemotherapeutic drugs are associated with drug resistance, cancer relapse, and side effects, scientists are turning to agents with more efficacy, such as natural compounds for treatment and prevention of BrCa. Selected natural compounds, substances derived from living organisms, promote apoptosis and inhibit metastasis, preventing cancer growth. As a result, these compounds have the potential to suppress BrCa progression, thus increasing patient survival rates and decreasing the number of BrCa-related deaths. In this review, we summarize natural compounds that have displayed, anti-cancer effects on BrCa cells in various studies. These natural compounds inhibit the development of BrCa, suppress the growth of cancer cells, and promote cell death. We conclude that natural compounds are efficient, effective and promising agents for treating BrCa other than therapeutic methods.

Cytotoxic and apoptotic inducing activity of Amoora rohituka leaf extracts in human breast cancer cells.

BACKGROUND: Amoora rohituka is described in Ayurveda, an Indian traditional system of medicine for management of disorders of blood, diseases of eye, helminthiasis disease, ulcer, liver disorders and splenomegaly. However, the leaves were not reported to have anticancer properties till date. OBJECTIVE: This study was carried out to evaluate the cytotoxic potential of leaf extracts of Amoora rohituka. MATERIALS AND METHODS: The leaves powder was macerated in petroleum ether, ethyl acetate and methanol and evaluated their anticancer activities in vitro. The phytochemical constituents of the active (ethyl acetate) extract were screened by FTIR analysis and phytochemical screening methods. RESULTS: The ethyl acetate extract (RLEA) showed the presence of alkaloids, flavonoids, steroids, tannins, saponins and terpenoids. The RLEA exhibited high cytotoxic effect against human breast cancer cells, MCF-7 (IC50 = 9.81 µg/mL) and induced apoptosis by altering nuclear morphology and DNA laddering. Wound healing assays explained the potency of extract to decrease the cell migration. CONCLUSION: The extract of Amoora rohituka leaves exhibited anticancer activity with less toxicity and it could be used for development of alternative drugs in the treatment of human breast cancer.

Characterization and evaluation of mycosterol secreted from endophytic strain of Gymnema sylvestre for inhibition of α-glucosidase activity.

Endophytic fungi produce various types of chemicals for establishment of niche within the host plant. Due to symbiotic association, they secrete pharmaceutically important bioactive compounds and enzyme inhibitors. In this research article, we have explored the potent α-glucosidse inhibitor (AGI) produced from Fusarium equiseti recovered from the leaf of Gymnema sylvestre through bioassay-guided fraction. This study investigated the biodiversity, phylogeny, antioxidant activity and α-glucosidse inhibition of endophytic fungi isolated from Gymnema sylvestre. A total of 32 isolates obtained were grouped into 16 genera, according to their morphology of colony and spores. A high biodiversity of endophytic fungi were observed in G. sylvestre with diversity indices. Endophytic fungal strain Fusarium equiseti was identified through DNA sequencing and the sequence was deposited in GenBank database (https://ncbi.nim.nih.gov) with acession number: MF403109. The characterization of potent compound was done by FTIR, LC-ESI-MS and NMR spectroscopic analysis with IUPAC name 17-(5-ethyl-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] phenanthren-3-ol. The isolated bioactive compound showed significant α-amylase and α-glucosidase inhibition activity with IC50 values, 4.22 ± 0.0005 µg/mL and 69.72 ± 0.001 µg/mL while IC50 values of acarbose was 5.75 ± 0.007 and 55.29 ± 0.0005 µg/mL respectively. This result is higher in comparison to other previous study. The enzyme kinetics study revealed that bioactive compound was competitive inhibitor for α-amylase and α-glucosidase. In-silico study showed that bioactive compound binds to the binding site of α-amylase, similar to that of acarbose but with higher affinity. The study highlights the importance of endophytic fungi as an alternative source of AGI (α-glucosidase inhibition) to control the diabetic condition in vitro.

Neuroprotective Activity of Evolvulus alsinoides & Centella asiatica Ethanolic Extracts in Scopolamine-Induced Amnesia in Swiss Albino Mice.

AIM: To carry out the comparative nootropic, neuroprotective potentials of two medicinal plant species. MATERIAL AND METHODS: For neuroprotective activity; behavior models (elevated plus maze & morris water maze), in vivo antioxidant (superoxide dismutase, catalase, lipid peroxidation & reduced glutathione), inflammatory markers (IL-1ß, IL-6 & TNF-α) and acetylcholine esterase (AChE) assessment procedures followed at different dosages i.e. 250 & 500 mg/kg of Evolvulus alsinoides and Centella asiatica ethanolic extracts. At the end of the study, it was performed histopathological analysis of the following organs: brain, heart, liver, and kidney. RESULTS: In oral administration of different doses of ethanolic extracts of both medicinal plants i.e. Sco + EEA 250 = 2.49 ± 0.29 , Sco + EEA 500 = 2.67 ± 0.36, Sco + ECA 250 = 2.33 ± 0.17, Sco + ECA 500 = 2.77 ± 0.21, Sco + EEA + ECA 250 = 2.61 ± 0.32 and Sco + EEA + ECA 500 = 2.79 ± 0.16 U/mg of protein respectively against the scopolamine induced group Sco (control) = 5.51 ± 0.35 U/mg of protein extracts shows neuroprotective and nootropic activity with reducing AChE level in the brain homogenate of swiss albino mice. CONCLUSION: Since the E. alsinoides & C. asiatica are already used in traditional Indian medicine as the neuroprotective agent and also found promising effects over inflammatory diseases, wound healing, and immunomodulatory activity. The neuroprotective effect of both plants extracts attributed to inhibition of AChE activity and improve the spatial memory formation.

Effect of selenium on connexin expression, angiogenesis, and antioxidant status in diabetic wound healing.

This study was done to analyze the effect of selenium on antioxidant status and expression of different connexins in diabetic wound healing. The levels of vascular endothelial growth factor, superoxide dismutase, lipid peroxide, and connexins were analyzed in wound tissues taken from diabetic and non-diabetic mice before and after sodium selenite administration. The mRNA transcript levels of Cx 26, 30.3, 31, 31.1, and 43 were significantly elevated in diabetic wounds as compared to the non-diabetic wounds. After selenium administration, the expression of connexins along with serum glucose decreases more significantly in diabetic wounds as compared to non-diabetic wounds. In diabetic wounds, the low levels of vascular endothelial growth factor and extracellular superoxide dismutase were restored to normal level following selenium administration. The lipid peroxidation decreased significantly in diabetic mice post-selenium administration. The histopathological analysis revealed that administration of selenium improves angiogenesis at the wound site. The results of this study demonstrate that selenium, acting as an essential component of the antioxidant system, normalizes the antioxidant status, and as an insulin mimetic compound, downregulates connexin expressions and induces angiogenesis. Together, these effects of selenium accelerate wound healing in diabetic conditions.

Evidence-based Critical Evaluation of Glycemic Potential of Cynodon dactylon.

The present study is an extension of our previous work carried out on Cynodon dactylon. This study deals with the critical evaluation of glycemic potential of ethanolic extract of defatted C. dactylon. The doses of 250, 500 and 750 mg kg(-1) bw of the extract were administered orally to normal as well as Streptozotocin-induced diabetic rats to study its glycemic potential. The effect of repeated oral administration of the same doses of ethanolic extract was also studied on serum lipid profile of severely diabetic (SD) rats. The dose of 500 mg kg(-1) bw was identified as the most effective dose as it lowered the blood glucose levels of normal by 42.12% and of diabetic by 43.42% during fasting blood glucose (FBG) and glucose tolerance test respectively. The SD rats were also treated daily with this identified dose of 500 mg kg(-1) bw for 2 weeks and a significant reduction of 56.34% was observed in FBG level. Total cholesterol, low density lipoprotein and triglyceride levels were also decreased by 32.94, 64.06 and 48.46% respectively in SD rats whereas, cardioprotective high density lipoprotein increased by 16.45%. The reduced urine sugar level and increased body weight are additional advantages. These evidences clearly indicate that the ethanolic extract of defatted C. dactylon has high antidiabetic potential along with good hypolipidemic profile.

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals.

Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. Previously, we have demonstrated potent hypoglycemic activity of lyophilized aqueous extract of Murraya koenigii leaves in normal and alloxan induced diabetic rabbits for short duration of 6 h. In this study, we examined the effect of 1 month oral administration of Murraya koenigii aqueous leaves extract in normal and STZ induced severe diabetic rats, at the dose of 300 mg/kg bw, on various biochemical parameters, viz., fasting blood glucose (FBG), total cholesterol (TC), HDL-cholesterol (HDL), triglyceride (TG), alkaline phosphatase (ALKP), serum glutamate oxaloacetate and pyruvate transaminases (SGOT and SGPT) and serum creatinine. In case of diabetic animals fasting blood glucose (FBG) levels of treated animals reduced by 48.2% after 30 days treatment with the aqueous leaves extract. A fall of 19.2 and 30.8% in TC and 22.97 and 37.1% in TG levels were also observed in the case of treated normal as well as diabetic rats, respectively. Feeding the extract increased the HDL-cholesterol level by 16 and 29.4% in normal and diabetic rats, respectively, as compared with their initial values. In the normal rats after 1 month of oral administration of the extract SGOT and SGPT levels were decreased by 21.7 and 25.0%. Serum alkaline phosphatase values of the treated normal animals were also reduced by 33% while negligible change was observed in the normal control animals. In the case of diabetic rats, SGOT and SGPT levels were reduced by 36.7 and 32.2%, respectively, whereas ALKP levels decreased by 39.7% after 1 month oral administration of the extract. The serum creatinine levels decrease in normal as well as in the diabetic animals by 17.75 and 18.2%, respectively, as compared to initial values. In the diabetic control animals the urinary sugar remains at +4 level but there was a decrease of 75% in urine sugar in the case of treated diabetic rats. This indicates that the aqueous extract of Murraya koenigii has favorable effect in bringing down the severity of diabetes.

Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats.

Aegle marmelos Corr. (Rutaceae) is widely used in Indian Ayurvedic medicine for the treatment of diabetes mellitus. The aqueous extract of Aegle marmelos seeds was administered orally at different doses (100, 250 and 500 mg/kg) to normal as well as sub (fasting blood glucose (FBG) normal; glucose tolerance abnormal) and mild (FBG 120-250 mg/dl) diabetic rats. The dose of 250 mg/kg was found to be most effective dose and it decreases blood glucose level (BGL) by 35.1% in normal healthy rats after 6h of administration. The same dose also showed a marked reduction in BGL of 41.2% in sub and 33.2% in mild diabetic rats in glucose tolerance test (GTT) after 2 h. Treatment of severely (FBG >250 mg/dl) diabetic rats for 14 days with a dose of 250 mg/kg reduces the fasting blood glucose by 60.84% and urine sugar by 75% than their pretreatment levels. It brought about fall in level of total cholesterol (TC) by 25.49% with increase of 33.43% in high density lipoprotein (HDL) and decrease of 53.97 and 45.77% in low density lipoprotein (LDL) and triglyceride (TG), respectively. These results clearly indicate that aqueous seed extract of Aegle marmelos possess antidiabetic and hypolipidemic effects in diabetic rats.