Green synthesis of silver nanoparticles from Euphorbia milii plant extract for enhanced antibacterial and enzyme inhibition effects.

Objectives: Silver nanoparticles (AgNPs) are gaining increasing attention in biomedical applications due to their unique properties. Green synthesis methods are environmentally friendly and have demonstrated potential for AgNP production. This study explores the green synthesis of AgNPs using the methanolic extract of Euphorbia milii, a plant known for its medicinal properties. The primary objectives of this research were to synthesize AgNPs using E. milii extract, characterize the nanoparticles (NPs) using various techniques, and evaluate their antibacterial and enzyme inhibitory activities. Methods: E. milii plant extract was utilized for the green synthesis of AgNPs. The characterization of the NPs was performed through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy (EDX). Antibacterial activity was assessed against Staphylococcus aureus, while enzyme inhibitory assays were conducted against urease, α-glucosidase, carbonic anhydrase II, and xanthine oxidase. Results: The synthesized AgNPs exhibited significant antibacterial effects, with a remarkable 20-mm zone of inhibition against S. aureus, surpassing the efficacy of the plant extract alone. Furthermore, the AgNPs demonstrated remarkable enzyme inhibition, achieving impressive percentages of 77.98% against α-glucosidase and 88.54% against carbonic anhydrase II. Half-maximal inhibitory concentration values for enzyme inhibition were highly promising, including 78.09 ± 1.98 µM for α-glucosidase, 0.22 ± 0.10 µM for carbonic anhydrase II, and 7.11 ± 0.55 µM for xanthine oxidase. Conclusion: In this study, AgNPs were successfully synthesized using E. milii extract and characterized using various techniques. The AgNPs exhibited significant antibacterial and enzyme-inhibitory activities, showcasing their potential for biomedical applications.

Erratum to "In-vitro antioxidant, lipoxygenase inhibitory, and in-vivo muscle relaxant potential of the extract and constituent isolated from Diospyros kaki (Japanese Persimmon)"[Heliyon Volume 9, Issue 3, MARCH 2023, Article e13816].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13816.].

In-vitro antioxidant, lipoxygenase inhibitory, and in-vivo muscle relaxant potential of the extract and constituent isolated from Diospyros kaki (Japanese Persimmon).

Diospyros kaki (Japanese persimmon) is cultivated specious of the Diospyros genus. D. kaki is a multi-medicinal application in the folk system for the cure of ischemic stroke, angina, atherosclerosis, muscle relaxation, internal hemorrhage, hypertension, high cough, and infectious disease. The main objective of this study was the isolated bioactive metabolites from chloroform fractions of D. kaki. The extract and fractions were then tested for various in-vitro (antioxidant and lipoxygenase) and in-vivo (muscle relaxant) activities. The repeated chromatographic separation of chloroform extract afforded compound 1. Compound 1, n-hexane, and chloroform fractions were evaluated for in vitro antioxidant, lipoxygenase inhibitory, and in vivo muscle relaxant potency. The chloroform extract has 79.54% interaction with DPPH at higher concentrations (100 µg/ml) while the compound exhibited a maximum effect of 95.09% at 100 µg/ml. Compound 1 exhibited significant lipoxygenase inhibitory activity with an IC50 value of 36.98 µM followed by a chloroform extract of 57.09 µM. Similarly, compound 1 and chloroform extract showed excellent muscle relaxant effects at a higher dose. From this investigation, it is concluded that extracts and pure compounds exhibited promising antioxidant, lipoxygenase inhibitory, and muscle relaxant activity. This study excellently rationalizes the traditional usage of D. kaki in curing various diseases. Furthermore, the docking results indicate, that the isolated compound fits well into the active site of the lipoxygenase, and makes strong interactions with the target protein.

Therapeutic potential of herbal medicine for the management of hyperlipidemia: latest updates.

Hyperlipidemia, the most common form of dyslipidemia, is the main source of cardiovascular disorders, characterized by elevated level of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) with high-density lipoprotein cholesterol (HDL-C) in peripheral blood. It is caused by a defect in lipid metabolism in the surface of Apoprotein C-II or a defect in lipoprotein lipase activity as well as reported in genetic, dietary and environmental factors. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE and CNKI Scholar. The current review focused on the risk factors of dyslipidemia, synthetic medication with their side effects and different types of medicinal plants having significant potential for the management of hyperlipidemia. The management of hyperlipidemia mostly involves a constant decrease in lipid level using different remedial drugs like statin, fibrate, bile acid sequestrates and niacin. However, this extensive review suggested that the consequences of these drugs are arguable, due to their numerous adverse effects. The selected parts of herb plants are used intact or their extracts containing active phytoconstituents to regulate the lipids in blood level. It was also noted that the Chinese herbal medicine and combination therapy is promising for the lowering of hyperlipidemia. This review intends to provide a scientific base for future endeavors, such as in-depth biological and chemical investigations into previously researched topics.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties.

The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

In Vivo and In Silico Studies of Flavonoids Isolated from Pistacia integerrima as Potential Antidiarrheal Agents.

Pistacia integerrima leaf galls are used in several traditional medicines to cure many diseases such as diarrhea, asthma, fever, cough, vomiting, and hepatitis. The main goal of the present investigation was to assess the antidiarrheal effect of the Pistacia integerrima extracts/fractions and four isolated flavonoid compounds (1-4) on mice. An in vivo assay involving castor-oil-induced diarrhea was used to evaluate the antidiarrheal potential of extracts/fractions at 100, 200, and 400 mg/kg p.o., as well as isolated compounds at 5, 10, and 20 mg/kg p.o. Pretreatment of mice with extracts/fractions significantly attenuated castor-oil-induced diarrhea in a dose-dependent manner. Among all crude extracts and fractions, the ethyl acetate extract was the most effective with 100% protection against diarrhea followed by chloroform (75% protection) at 400 mg/kg p.o. Although all the isolated compounds exhibited strong antidiarrheal activity, isolated compounds 1 and 4 demonstrated 100% protection against diarrhea. Moreover, docking models were performed using the Molecular Operating Environment (MOE) and AutoDock software and suggested that the extracts and isolated compounds exert antidiarrheal activity by inhibiting mu-opioid and delta-opioid receptors. Therefore, our finding affords a strong pharmacological basis for the traditional use of P. integerrima galls in the treatment of diarrhea.

Sedative-hypnotic effect and in silico study of dinaphthodiospyrols isolated from Diospyros lotus Linn.

Traditionally, Diospyros lotus Linn is used for insomnia and other associated disorders. Insomnia is a worldwide disorder with different etiology which is treated with different synthetic medicine associated with addiction. Natural products are generally devoid of such addition with good efficacy. Current research was conducted to evaluate the sedative and hypnotic effects of dimeric naphthoquinones such as dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5) and dinaphthodiospyrol F (6) isolated from the chloroform fractions of D. lotus. The sedative and hypnotic effects at the dose of 5 and 10 mg/kg (each compound) were assessed through open field and phenobarbital induced sleep test, respectively. In the case of open field test the administration of tested compounds significantly hindered the movement of animals, while in case of hypnotic effect the tested samples significantly improved the onset and duration of sleep as compared to control. The overall effects were in a dose dependent manner. The compounds were also assessed for acute toxicity, but no toxicity was observed. In this regard, our research triumphantly announced the strong chemical base for the folkloric values of the plant with their fringe benefits and implemented a platform for further aspects of mechanistic and clinical studies. A possible mechanism of in vivo inhibition was studied by using docking simulations on GABA receptors. Binding orientations and types of interactions revealed that a possible mechanism behind these pharmacological actions might be interaction with GABA receptors.

In Vivo Anti-inflammatory, Analgesic, and Sedative Studies of the Extract and Naphthoquinone Isolated from Diospyros kaki (Persimmon).

Anti-inflammatory, analgesic, and sedative medicine is used with numerous side effects, including peptic ulcer, headache, addiction, and other complications. In this regard, discovery research is undergoing a process to discover effective, safe, and economical drugs with no side effects. The aim of this study was to assess chloroform extracts and isolated compounds for anti-inflammatory, analgesic, and sedative activities in animal models. The anti-inflammatory potential was measured by using the carrageenan-induced and histamine-induced paw edema procedure, while the analgesic potential was determined using a hot plate analgesiometer. The sedative effect was observed in an animal model for screening of the locomotor effect of the extract and isolated compound 1. Our data exhibited that the extract and compound 1 attenuated carrageenan-induced and histamine-induced paw edema (93.98 and 89.54%, respectively). Furthermore, compound 1 attenuated biphasic edema associated with histamine and prostaglandins. The chloroform extract showed a moderate analgesic effect; however, compound 1 showed a significant analgesic potential (p < 0.001) by increasing the latency time of the animals in the thermally induced algesia model. Compound 1 exhibited a significant sedative effect and dose-dependent analgesic activity. It is concluded that the chloroform extract and compound 1 showed remarkable anti-inflammatory, analgesic, and sedative activities. This research work strongly rationalizes the folkloric usage of Diospyros kaki in the treatment of inflammation, pain, and insomnia.

Evaluation of the anti-diarrheal effects of the whole plant extracts of Cuscuta reflexa Roxb in pigeons.

BACKGROUND: Cuscuta reflexa (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity of C. reflexa was evaluated in pigeons (Columba livia) using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts. METHODS: The antidiarrheal effect of C. reflexa was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) and 1 mL/kg (2%), CRAE (50, 100 and 200 mg/kg) and CRME (50, 100 and 200 mg/kg) were administered intramuscularly at different doses into each pigeon in the test groups. RESULTS: In addition to cisplatin-induced diarrhea, all paradigms tested gave significant results (P < 0.01). The JCR, at different doses, exhibited a significant (p < 0.01) a dose-dependent antidiarrheal effect on both the frequency and the onset of diarrhea. Similarly, CRAE and CRME, at doses of 100 and 200 mg/kg, showed considerable (p < 0.001) inhibition against the onset and frequency of diarrhea. On the other hand, JCR, CRAE, and CRME exerted significant effects (p < 0.001) on the percentage inhibition (PI) of diarrhea and gastrointestinal charcoal transit in a dose-dependent manner. In this respect, the maximum PI (p < 0.01) of JCR, CRAE, and CRME in different experimental paradigms was 43.13, 49.14, and 55.99 %, respectively. CONCLUSIONS: Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of C. reflexa in folk medicine as an antidiarrheal medicinal plant.

Green synthesis, in vivo and in vitro pharmacological studies of Tamarindus indica based gold nanoparticles.

The current investigation aims to synthesize gold nanoparticles (AuNPs) from aqueous extract of Tamarindus indica and to evaluate the in vitro anti-bacterial and in vivo sedative and anelgescic activities of crude extract as well as synthesized AuNPs. Several methods have been reported to synthesize AuNPs; however, most of them were not ecofriendly. In the present study, the green synthesis of AuNPs has been carried out. Using the green synthesis method, AuNPs of T. indica were synthesized at room temperature (25 °C) by mixing 5 mL of HAuCl4 (1 mM) with 1 mL of T. indica seed extract solution. This extract solution was prepared by taking 5 gm dry seeds in 100 mL of double deionized water with continuous stirring for up to 24 h at 80 °C. The stability of AuNPs was confirmed with the help of relevant experimental techniques including ultraviolet-visible (UV/Vis) showing maximum absorbance at 535-540 nm, Fourier transform infrared showing a broad signal at 3464 cm-1 which can be attributed to either amide or hydroxyl functionalities and atomic force microscopy analysis showed that the biomaterial surrounding AuNPs was agglomerated which proves the formation of discrete nanostructutres. These AuNPs have been evaluated for their antibacterial potential. The results revealed good antibacterial activity of the samples against. Klebsiella pneumonia, Bacillus subtilis and Staphylococcus epidermidis with 10-12 mm zone of inhibition range. The AuNPs were also found stable at high temperature, over a range of pH and in 1 mM salt solution. Moreover, the crude extract and respective AuNPs also exhibited interesting sedative and analgesic activities. Hence, we focused on phytochemicals-mediated synthesis of AuNPs considered as greatest attention in the treatment of anti-bacterial, analgesic, and sedative.

Novel Anticancer Dimeric Naphthoquinones from Diospyros lotus having Anti- Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence.

BACKGROUND: Cancer being a genetically heterogeneous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. OBJECTIVE: The current study focused on the anticancer potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. METHODS: In vitro Epstein-Barr-Virus (EVA) an early antigen activation assay was used to evaluate the antitumor potential of tested compounds followed by a two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance reversal potential. The in vitro heatinduced protein denaturation assay was used for the anti-inflammatory effect of the tested compounds. RESULTS: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In a two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th week, whereas compound 2 exerted the same effect at 13th week, while both provoked 100% effect at 20th week. Both compounds significantly attenuated thermal-induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of Multidrug-Resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR reversal effect in a dose-dependent manner against mouse T-lymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. CONCLUSION: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects with significant attenuation of thermal-induced denaturation of the protein. These compounds may explain the traditional uses of D. lotus which might be effective anticancer agents.

In vitro α-glycosidase and urease enzyme inhibition profile of some selected medicinal plants of Pakistan.

The current study aims at exploring enzyme inhibition of four species of medicinal herbs, namely Senna bicapsularis, Thevetia peruviana, Nerium oleander and Vinca major. Plant selection was done on the basis of their therapeutic uses by local practitioners. The crude methanolic extracts of these plants were tested for their α-glycosidase and urease enzyme inhibition potential. The observed urease inhibitory potential for the crude extract of S. bicapsularis, T. peruviana and N. oleander were 8.3 ± 0.33 µg, 6.98 ± 0.98 µg and 9.56 ± 1.43 µg, respectively while the V. major did not show any inhibition. In addition, the IC50 value for Thiourea was 22.3 ± 1.14 µg. The crude extracts of S. bicapsularis, T. peruviana, N. oleander, V. major were shown to inhibit α-glycosidase activity with an IC50 value of 630.3 ± 0.03 µg, 700.7 ± 2.43 µg, 430.4 ± 3.97 µg, and the standard (acarbose) 880 ± 1.03  µM, respectively. Based on the TLC profile, the extract of S. bicapsularis was subjected to column chromatography and the major component named rhein (1) was identified. Compound 1 exhibited excellent urease and α-glycosidase inhibitory activity with an IC50 value of 7.4 ± 0.32 and 622.3 ± 1.03 µM, respectively.

Anti-inflammatory and In Silico Docking Studies of Heterophragma adenophyllum Seem Stem Constituents.

Heterophragma adenophyllum is a traditional medicinal plant that has been used as anti-inflammatory and to relief muscular tension. In the current research, four isolated constitutes namely lapacho (1), peshawaraquinone (2), indanone derivatives (3), α-lapachone (4) of H. adenophyllum were tested for anti-inflammatory effect using the carrageenan- and histamine-induced paw edema paradigm. The tested compounds (1-4) were evaluated for anti-inflammatory effect during the early and late phase of edema induction. In the early phase, all tested compounds (0.5 2.5 mg/kg each i.p.) demonstrated less than 50% effect, while in the later phase, compounds (2 and 3) demonstrated 85.66 and 89.87% attenuation. In addition, compounds (1-4) were subjected to histamine-induced inflammation, where compounds 2 and 3 exhibited excellent effects 86.87 and 89.98%, respectively at 5 mg/kg after the 2nd hour of administration, whereas compounds 1 and 4 did not exhibit any significant effect as compared with the negative control. Molecular docking results revealed a very high potency of compound based on the protein-ligand interaction (PLI) profile, which was further evaluated through a molecular dynamic simulation study. Therefore, the anti-inflammatory effect of H. adenophyllum attributed to the presence of these bioactive compounds (1-4) strongly supports the traditional uses of H. adenophyllum for treatment of inflammation. However, compounds 2 and 3 which exerted anti-inflammatory effect must be subjected for further mechanistic studies.

Gastrointestinal Motility, Muscle Relaxation, Antipyretic and Acute Toxicity Screening of Amyrin Type Triterpenoid (Daturaolone) Isolated From Datura metel Linnaeus (Angel's Trumpet) Fruits.

Datura metel Linn is used traditionally for the treatment of various diseases including relaxation of smooth muscles, relief of fever, as well as gastrointestinal disorder. This study deals with the bio-guided isolation of an active, amyrin-type triterpenoid, namely 3-oxo-6-ß-hydroxy-ß-amyrin (daturaolone; 1), from the chloroform fraction of Datura metel L. (Angel's trumpet) fruits and its gastrointestinal motility, antipyretic, and muscle relaxation effects in animal models. The chemical structure of daturaolone (1) was elucidated by NMR spectroscopy and crystallography techniques. The chloroform fraction and daturaolone (1) were assessed for the GIT motility test. Data exhibited in charcoal meal GI transit test show that chloroform fraction and daturaolone (1) significantly reduce GIT motility and increased intestinal transit time, comparable to the standard (atropine), a muscarinic receptor blocking agent. Muscle relaxant potency of the extract and daturaolone (1) was assessed in various animal paradigms. In the inclined plane screening test, it produced a significant (P < 0.05) muscle relaxation potential in a dose-dependent manner after 30, 60, and 90 min. Likewise, the muscle relaxation potential of the extract and daturaolone (1) was strongly complemented by the chimney and traction test, representing a dominant effect after 60 min of sample administration. The chloroform fraction showed good antipyretic activity, and while daturaolone (1) exhibited significant activity at a higher dose, the maximum effect (84.64%) was at 20 mg/kg i.p. In acute toxicity screening test, the chloroform extract (100, 250, 500, and 1,000 mg/kg) and daturaolone (1) (5, 10, 20, and 50 mg/kg) were found safe. In conclusion, the chloroform extract and daturaolone (1) exhibited strong gastrointestinal motility, muscle relaxation, and antipyretic activity in different animal models and intestinally, was found safe at higher tested doses.

Therapeutic potentials of crocin in medication of neurological disorders.

Neurological sicknesses are serious, multifactorial, debilitating disorders that may cause neurodegeneration. Neuroprotection is the protection of the structure and capacity of neurons from affronts emerging from cell injuries instigated by an assortment of specialists or neurodegenerative diseases. Various neurodegenerative diseases, including Alzheimer's, Parkinson's, and epilepsy, afflict many people worldwide, with increasing age representing the leading risk factor. Crocin is a natural carotenoid compound which was found to have therapeutic potentials in the management of the neurological disease. In this review, we focused on the restorative capabilities of Crocin as a neuroprotective agent. The general neuroprotective impact and the various conceivable basic components identified with Crocin have been examined. In light of the substantial proof indicating the neuro-pharmacological viability of Crocin to different exploratory standards, it is concluded that Crocin exerts direct antioxidant, antiapoptotic and anti-inflammatory activities by multiple signaling pathways. Besides, Crocin was found to elevate dopamine level in the brain during the experimental model of Parkinson's disease. Thus, this compound has been demonstrated to be a promising option for the treatment of neurodegenerative diseases, with few adverse effects. It ought to be further considered as a potential contender for neuro-therapeutics, concentrating on the mechanistic and clinical evidence for its effects.

Potent In Vitro α-Glucosidase and ß-Secretase Inhibition of Amyrin-Type Triterpenoid Isolated from Datura metel Linnaeus (Angel's Trumpet) Fruits.

This study deals with α-glucosidase and ß-secretase inhibitory screening of extract/fractions and isolated daturaolone (1), namely, 3-oxo-6-ß-hydroxy-ß-amyrin (daturaolone) from chloroform fraction of Datura metel L. Among entire fractions, the chloroform soluble fraction showed excellent activity against α-glucosidase with % inhibition 90.8 with IC50160.2 ± 1.85 µg and daturaolone (1) with 98.7% inhibition with IC50840.4 ± 1.74 µM, respectively. Similarly, extract and daturaolone (1) also exhibited significant activity against the ß-secretase enzyme (BACE1) with % activities 88.27 and 95.19 and with IC50 values 304.21 ± 2.98 µg and 260.70 ± 1.87 µM, respectively, as compared to the standard inhibitor (Ans670, Sta671, Val672)-amyloid-ß/A4 precursor protein 770 fragments 662-675) with % activity 94.21 and IC50 value 289.24 ± 1.60 µM. This finding encourages and opens a new window for further detail phytochemical investigation on D. metel in order to isolate novel compounds with promising enzyme inhibitory potential.

Effect of nanostructured lipid carriers on transdermal delivery of tenoxicam in irradiated rats.

Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is an effective route of drug administration, as it directs the drug to the inflamed site with reduced incidence of systemic adverse effects such as gastric hemorrhage and ulcers. Tenoxicam (TNX) is a member of NSAIDs that are marketed only as oral tablets due to very poor absorption through the skin. The current study intended to formulate and characterize a hydrogel loaded with nanostructured lipid carriers (NLCs) to enhance the transdermal delivery of TNX. Six formulations of TNX were formulated by slight modifications of high shear homogenization and ultrasonication method. The selected formula was characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo skin permeation studies. Moreover, the effectiveness of the developed formula was studied in-vivo using carrageenan-induced paw edema and hyperalgesia model in irradiated rats. Formula F4 was chosen from six formulations, as the average diameter was 679.4 ± 51.3 nm, PDI value of about 0.02, zeta potential of -4.24 mV, EE of 92.36%, globules nanoparticles without aggregations and absence of interactions in the developed formula. Additionally, the in-vivo study showed the efficacy of formula F4 (TNX-NLCs hydrogel) equivalent to oral TNX in reducing the exaggerated inflammatory response induced by carrageenan after irradiation. In conclusion, the present findings suggest that TNX-NLCs hydrogel could be a potential transdermal drug delivery system alternative to the oral formulation for the treatment of various inflammatory conditions.

In vivo analgesic, anti-inflammatory, and sedative activity and a molecular docking study of dinaphthodiospyrol G isolated from Diospyros lotus.

BACKGROUND: Analgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product from Diospyros lotus, was tested for the aforementioned bioactivities. OBJECTIVES: To evaluate analgesic, anti-inflammatory, and sedative potential of D. lotus extracts in animal paradigms using BALB/c mice as experimental model. METHODS: Analgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction of D. lotus were evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound 1. Compound 1 was also subjected to molecular modeling studies against cyclooxygenase enzymes. RESULTS: Results from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p < 0.001) and dose-dependent antinociceptive and sedative effects were demonstrated by the isolated compound. Molecular docking and dynamics simulation studies of the isolated compound against cyclooxygenase enzyme indicated that compound 1 forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor. CONCLUSIONS: Compound 1 exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use of D. lotus in the treatment of inflammation, pain, and insomnia.

Hepcidin, an overview of biochemical and clinical properties.

Hepcidin is a peptide hormone which helps in regulating iron homeostasis in the human body. Iron obtained from daily diet is passed through the intestinal enterocyte apical membrane via divalent metal transporter 1 (DMT1), which is either stored as ferritin or moved into the plasma by hepcidin-ferroportin (Fpn) as an exporter. Hepcidin (hepatic bactericidal protein) is a cysteine rich peptide, was initially identified as a urinary antimicrobial peptide. It contains 25 amino acids and four disulfide bridges. It has significant role in regulation of iron in the body. Stimulation of iron in plasma and further its storage is linked with the production of hepcidin. This enhancement of iron hampers the absorption of iron from the diet. The cause of hereditary recessive anemia also known as Iron-refractory iron deficiency anemia (IRIDA) is characterized by increased hepcidin production due to a gene mutation in the suppressor matriptase-2/TMPRSS6. During infection, hepcidin plays a defensive role against various infections by depleting the extracellular iron from the body. Moreover, hepcidin lowers the concentrations of iron from the duodenal enterocytes, macrophages and also decrease its transport across the placenta.This review highlights the significant role of hepcidin in the iron homeostasis and as an antimicrobial agent.

In-vitro and in-silico anticancer potential of taxoids from Taxus wallichiana Zucc.

INTRODUCTION: Natural products derived from medicinal plants provide beneficial cancer chemotherapeutic drugs. Bioactive constituents from plants are explored for their anticancer properties. METHODS: Three known compounds (deacetylbaccatin III, tasumatrol B, and taxawallin J) were isolated from Taxus wallichiana. Compounds were screened against four cancer cell lines, such as eA498, HepG2, NCI-H226, and MDR 2780AD. Cytotoxic activity was evaluated using MTT assay against cancer cell lines. RESULTS: Tasumatrol B showed good cytotoxic activity conducted for the improvement of inhibiting potential of these compounds against the cancer drug target protein (EGFR tyrosine kinase enzyme). The docking study showed that all compounds have binding affinities and interaction profile with the receptor tyrosine kinase. DISCUSSION: The study suggests that these compounds could be used for the discovery of novel inhibitors against the target receptors for the treatment of cancer.