Gentisic acid prevents colorectal cancer metastasis via blocking GPR81-mediated DEPDC5 degradation.

BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.

Assessing the health risks of heavy metals and seasonal minerals fluctuations in Camellia sinensis cultivars during their growth seasons.

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.

Neuroprotective potentials of Lead phytochemicals against Alzheimer's disease with focus on oxidative stress-mediated signaling pathways: Pharmacokinetic challenges, target specificity, clinical trials and future perspectives.

BACKGROUND: Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aß) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression. PURPOSE: This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds. METHODS: Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources. RESULTS: Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors. CONCLUSIONS: Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aß load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.

Mitigation of sciatica injury-induced neuropathic pain through active metabolites derived from medicinal plants.

Sciatica characterized by irritation, inflammation, and compression of the lower back nerve, is considered one of the most common back ailments globally. Currently, the therapeutic regimens for sciatica are experiencing a paradigm shift from the conventional pharmacological approach toward exploring potent phytochemicals from medicinal plants. There is a dire need to identify novel phytochemicals with anti-neuropathic potential. This review aimed to identify the potent phytochemicals from diverse medicinal plants capable of alleviating neuropathic pain associated with sciatica. This review describes the pathophysiology of sciatic nerve pain, its cellular mechanisms, and the pharmacological potential of various plants and phytochemicals using animal-based models of sciatic nerve injury-induced pain. Extensive searches across databases such as Medline, PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar were conducted. The findings highlights 39 families including Lamiaceae, Asteraceae, Fabaceae, and Apocyanaceae and Cucurbitaceae, effectively treating sciatic nerve injury-induced pain. Flavonoids made up 53% constituents, phenols and terpenoids made up 15%, alkaloids made up 13%, and glycosides made up 6% to be used in neuorpathic pain. Phytochemicals derived from various medicinal plants can serve as potential therapeutic targets for both acute and chronic sciatic injury-induced neuropathic pain.

The therapeutic effects of berberine for gastrointestinal cancers.

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers.

Managing Weed-Crop Interactions Enhances Chickpea (Cicer arietinum L.) Chemical Components.

Chickpea (Cicer arietinum L.) is a major pulse crop worldwide, renowned for its nutritional richness and adaptability. Weeds are the main biotic factor deteriorating chickpea yield and nutritional quality, especially Asphodelus tenuifolius Cav. The present study concerns a two-year (2018-19 and 2019-20) field trial aiming at evaluating the effect of weed management on chickpea grain quality. Several weed management practices have been here implemented under a factorial randomized complete block design, including the application of four herbicides [bromoxynil (C7H3Br2NO) + MCPA (Methyl-chlorophenoxyacetic acid) (C9H9ClO3), fluroxypyr + MCPA, fenoxaprop-p-ethyl (C18H16ClNO5), pendimethalin (C13H19N3O4)], the extracts from two allelopathic weeds (Sorghum halepense and Cyperus rotundus), two mulches (wheat straw and eucalyptus leaves), a combination of A. tenuifolius extract and pendimethalin, and an untreated check (control). Chickpea grain quality was measured in terms of nitrogen, crude protein, crude fat, ash, and oil content. The herbicides pendimethalin (Stomp 330 EC (emulsifiable concentrate) in pre-emergence at a rate of 2.5 L ha-1) and fenoxaprop-p-ethyl (Puma Super 7.5 EW (emulsion in water) in post-emergence at a rate of 1.0 L ha-1), thanks to A. tenuifolius control, showed outstanding performance, providing the highest dietary quality of chickpea grain. The herbicides Stomp 330 EC, Buctril Super 40 EC, Starane-M 50 EC, and Puma Super 7.5 EW provided the highest levels of nitrogen. Outstanding increases in crude protein content were observed with all management strategies, particularly with Stomp 330 EC and Puma Super 7.5 EW (+18% on average). Ash content was highly elevated by Stomp 330 EC and Puma Super 7.5 EW, along with wheat straw mulching, reaching levels of 2.96% and 2.94%. Crude fat content experienced consistent elevations across all treatments, with the highest improvements achieved by Stomp 330 EC, Puma Super 7.5 EW, and wheat straw mulching applications. While 2018-19 displayed no significant oil content variations, 2019-20 revealed the highest oil content (5.97% and 5.96%) with herbicides Stomp 330 EC and Puma Super 7.5 EW, respectively, followed by eucalyptus leaves mulching (5.82%). The results here obtained are of key importance in the agricultural and food sector for the sustainable enhancement of chickpea grain's nutritional quality without impacting the environment.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

Molecular Aspects and Therapeutic Implications of Herbal Compounds Targeting Different Types of Cancer.

Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment.

Neuroprotective Potential of Bacopa monnieri: Modulation of Inflammatory Signals.

BACKGROUND: To date, much evidence has shown the increased interest in natural molecules and traditional herbal medicine as alternative bioactive compounds to fight many inflammatory conditions, both in relation to immunomodulation and in terms of their wound healing potential. Bacopa monnieri is a herb that is used in the Ayurvedic medicine tradition for its anti-inflammatory activity. OBJECTIVE: In this study, we evaluate the anti-inflammatory and regenerative properties of the Bacopa monnieri extract (BME) in vitro model of neuroinflammation. METHODS: Neuronal SH-SY5Y cells were stimulated with TNFα and IFNγ and used to evaluate the effect of BME on cell viability, cytotoxicity, cytokine gene expression, and healing rate. RESULTS: Our results showed that BME protects against the Okadaic acid-induced cytotoxicity in SH-SY5Y cells. Moreover, in TNFα and IFNγ primed cells, BME reduces IL-1ß, IL-6, COX-2, and iNOS, mitigates the mechanical trauma injury-induced damage, and accelerates the healing of wounds. CONCLUSION: This study indicates that BME might become a promising candidate for the treatment of neuroinflammation.

Antidepressant activity of phytochemicals of Mangifera indica seeds assisted by integrated computational analysis.

Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.

Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents.

The field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.

Uncovering the Anticancer Potential of Polydatin: A Mechanistic Insight.

Polydatin or 3-O-ß-d-resveratrol-glucopyranoside (PD), a stilbenoid component of Polygonum cuspicadum (Polygonaceae), has a variety of biological roles. In traditional Chinese medicine, P. cuspicadum extracts are used for the treatment of infections, inflammation, and cardiovascular disorders. Polydatin possesses a broad range of biological activities including antioxidant, anti-inflammatory, anticancer, and hepatoprotective, neuroprotective, and immunostimulatory effects. Currently, a major proportion of the population is victimized with cervical lung cancer, ovarian cancer and breast cancer. PD has been recognized as a potent anticancer agent. PD could effectively inhibit the migration and proliferation of ovarian cancer cells, as well as the expression of the PI3K protein. The malignancy of lung cancer cells was reduced after PD treatments via targeting caspase 3, arresting cancer cells at the S phase and inhibiting NLRP3 inflammasome by downregulation of the NF-κB pathway. This ceases cell cycle, inhibits VEGF, and counteracts ROS in breast cancer. It also prevents cervical cancer by regulating epithelial-to-mesenchymal transition (EMT), apoptosis, and the C-Myc gene. The objective of this review is thus to unveil the polydatin anticancer potential for the treatment of various tumors, as well as to examine the mechanisms of action of this compound.

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant.

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.

Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.

Among various cancers, breast cancer is the most prevalent type in women throughout the world. Breast cancer treatment is challenging due to complex nature of the etiology of disease. Cell division cycle alterations are often encountered in a variety of cancer types including breast cancer. Common treatments include chemotherapy, surgery, radiotherapy, and hormonal therapy; however, adverse effects and multidrug resistance lead to complications and noncompliance. Accordingly, there is an increasing demand for natural products from medicinal plants and foods. This review summarizes molecular mechanisms of signaling pathways in breast cancer and identifies mechanisms by which natural compounds may exert their efficacy in the treatment of breast cancer.

The hematological and histological studies for the hepatoprotective-like effect of the hydromethanolic extract and the fractions of Viola serpens Wall.

Traditionally, Viola serpens has been used in the treatment of several human disorders including liver diseases without any scientific evidence. As the current therapies are not very effective and face challenges of unwanted effects and patient compliance, therefore more effective and safe agents are highly needed. The current study aimed to evaluate the hepatoprotective potential of the crude extract and subsequent fractions of the whole plant in the in-vivo model using various hematological and histopathological parameters followed by an HPLC study for the identification of phenolic compounds. Rabbits (1000-1200 g) were used in the study. Paracetamol (2g) was used to induce hepatotoxicity in experimental rabbits. The plant extract was used in two doses (150 and 300 mg/kg body weights) for eight days. The hematological parameters AST, ALT and ALP values were determined along with the histopathology of the liver. Phenolic compounds were identified by high-performance liquid chromatography (HPLC) Agilent-1260 infinity from their retention time, UV spectra and available standards while quantification was done taking the percent peak area. The doses 150 and 300 mg/kg body weight seemed to be more effective. The hematological values and the histopathological slides show the hepatoprotective effect of the plant. Regeneration indicated the presence of nuclei, nuclear cleaning, prominent nucleoli, RBC's, central veins and plates of hepatocytes. The HPLC studies revealed the presence of a number of phenicol compounds. The crude extract and the subsequent fractions of the plant possess strong hepatoprotective activity, providing a scientific rationale for its uses in the treatment of liver toxicities.

Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice.

Acute kidney injury (AKI) causes a decrease in renal function which leads to failure in balancing electrolyte, fluid and acid-base homoeostasis. AKI is a damaging and life-threatening disorder, but it can be managed if identified earlier. This study aimed to investigate the possible nephroprotective effect of Helianthus annuus seeds extract against gentamicin (GM) induced nephrotoxicity in male mice. The control group (0.5 ml normal saline i.p.,), Gentamycin (GM) group (GM 100 mg/kg i.p), silymarin + GM group (silymarin 50 mg/kg and GM 100 mg/kg i.p.,), H. annuus extract (HAE) and GM, group (HAE 250 mg/kg and GM 100 mg/kg i.p), HAE2 + GM group (HAE2; 500 mg/kg and GM 100 mg/kg i.p) and H. annuus oil (HAO) + GM (HAO 2.5 ml/kg and GM 100 mg/kg i.p). Serum creatinine, urea and blood urea nitrogen (BUN) were significantly (P< 0.001) elevated in the GM group compared to the control group. The elevated level of serum creatinine, urea and BUN were decreased significantly (P<0.001) in groups treated with HAE and HAO extracts compared to the GM group. The kidney histopathological study from the GM group showed tubular necrosis, vacuolation and fibrosis. However, the animal that received HAE and HAO showed no tubular necrosis and vacuolation. Only mild inflammation was observed compared to the GM group. In conclusion, the extract caused marked radical scavenger and protected the kidney from oxidative damage of GM. H. annuus seeds contain strong antioxidant compounds, including flavonoids, phenolic acids, tocopherols and minerals, which could be responsible for the current show.

How Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic Insights and Possible Solutions.

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.

Phytochemical Profiling, Anti-Inflammatory, Anti-Oxidant and In-Silico Approach of Cornus macrophylla Bioss (Bark).

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla. C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC50 values of 09.54 µg/mL and 7.8 µg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla, Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC50 values were 93.35 µg/mL against COX-2 and 75.64 µg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future.