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.

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.

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.

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.

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.

Diospyros, an under-utilized, multi-purpose plant genus: A review.

The genus Diospyros from family Ebenaceae has versatile uses including edible fruits, valuable timber, and ornamental uses. The plant parts of numerous species have been in use as remedies in various folk healing practices, which include therapy for hemorrhage, incontinence, insomnia, hiccough, diarrhea etc. Phytochemical constituents such as terpenoids, ursanes, lupanes, polyphenols, tannins, hydrocarbons, and lipids, benzopyrones, naphthoquinones, oleananes, and taraxeranes have been isolated from different species of this genus. The biological activities of these plants such as antioxidant, anti-inflammatory, analgesic, antipyretic, anti-diabetic, antibacterial, anthelmintic, antihypertensive, cosmeceutical, enzyme-inhibitory etc. have been validated by means of an in vitro, in vivo, and clinical tests. As a rich reserve of pharmacologically important components, this genus can accelerate the pace of drug discovery. Accordingly, the aim of the present review is to survey and summarize the recent literature pertaining to the medicinal and pharmacological uses of Diospyros, and to select experimental evidence on the pharmacological properties of this genus. In addition, the review also aims at identifying areas that need development to make use of this genus, especially its fruit and phytochemicals as means for economic development and for drug discovery.

Sedative-hypnotic-like effect and molecular docking of di-naphthodiospyrol from Diospyros lotus in an animal model.

BACKGROUND: Diospyros lotus Linn commonly known as date-plum, or Caucasian persimmon has multiple uses in folk medicine. Various parts of this plant is used for alleviating lumbago, dysponea, hemorrhage, insomnia, and hiccup. The plant extracts possess a variety of biological activities, such as anti-inflammatory, sedative, febrifuge, anti-microbial, vermifuge, and anti-hypertensive. AIM/HYPOTHESIS: The aim of the present work is to investigate the sedative-hypnotic effect of a rare dimeric napthoquione 1 obtained from the chloroform soluble fraction of D. lotus extracts. METHODS: Compound 1, di-naphthodiospyrol at 5, 10, and 15mg/kg intraperitoneal doses was assessed for its in vivo sedative effect in an open-field using a phenobarbitone-induced sleeping time model. The geometry of di-naphthodiospyrol was also optimized with the aid of density functional theory. In addition, molecular docking of compound 1 was performed with the receptor GABAA. RESULTS: The animal protocol-based assay showed significant sedative-hypnotic-like effects of compound 1 at various test doses (5, 10, and 15mg/kg i.p.). Docking studies indicated that this compound interacts strongly with important residues in receptor GABAA. CONCLUSIONS: Results from this investigation reveal that compound 1 possesses sedative-hypnotic- like properties which can be of interest in therapeutic research.

In vivo and in silico sedative-hypnotic like activity of 7-methyljuglone isolated from Diospyros lotus L.

Diospyros lotus L. possesses different therapeutic activities such as antioxidant, anti-proliferative, anti-microbial and sedative. However, no studies on the sedative-hypnotic activity of 7-methyljuglone are reported. In the present study, we have evaluated in vivo the anxiolytic-hypnotic like effects of 7-methyljuglone in mice with open field and phenobarbitone-induced sleeping time tests. We have also assessed in silico the involvement of GABAA, GABAB and 5HT1 neurotransmission in its mechanism of action. The intraperitoneal administration of 7-methyljuglone (2.5-10mg/kg) reduce significantly the number of crossed lines in mice open field test and concomitantly it shown a significant activity in term of onset of sleeping time and also in its duration. Moreover, 7-methyljuglone demonstrated in silico an interesting interaction with GABAA but not GABAB and 5HT1binding sites. All of these results, taken together, 7-methyljuglone may be an innovative candidate for designing new pharmaceutical and therapeutic applications.

Urease inhibition potential of Di-naphthodiospyrol from Diospyros lotus roots.

The dimeric napthoquione 5,8,4'-trihydroxy-1'-methoxy-6, 6'-dimethyl-7,3'-binaphtyl-1,4,5',8'-tetraone (1) was isolated from the chloroform fraction of Diospyros lotus extract. Compound 1 was screened for its inhibitory effects against four enzymes: urease, phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin, and showed selective activity against urease enzyme with an IC50 value of 254.1 ± 3.82 µM as compared to the standard thiourea (IC50 = 21 ± 0.11 µM). Furthermore, in silico docking study was carried out to explain the molecular mechanism of compound 1 against the target receptor.

Gastrointestinal Motility and Acute Toxicity of Pistagremic Acid Isolated from the Galls of Pistacia integerrima.

BACKGROUND: Pistacia integerrima has many medicinal uses in therapeutic as well as folk medicine. P. integerrima has been used for the treatment of different ailments such as blood purifier, anti-inflammatory, and as remedy for gastrointestinal disorders such as vomiting and diarrhea, expectorant, cough, asthma and fever. OBJECTIVE: The main objective of this research work was to evaluate the effect of pistagremic acid (PA) isolated from the galls of Pistacia integerima in acute toxicity and gastrointestinal (GIT) motility tests. METHODS: Compound 1 namely pistagremic acid (PA) (at 10, 50, 100 mg/kg i.p) were assessed for their in-vivo gastrointestinal motility test using charcoal screening model. RESULTS: Results revealed that pretreatment of PA exhibited substantial safety in acute toxicity test up to the dose of 500 mg/kg p.o. However, when studied in charcoal meal GI transit test, PA caused significant (p < 0.05) attenuation of GIT motility and an increase in intestinal transit time, comparable to atropine (a muscarinic receptor blocking agent). CONCLUSION: In conclusion, PA displayed a strong dose-dependent reduction in GIT motility with considerable safety.

In vivo antinociceptive and muscle relaxant activity of leaf and bark of Buddleja asiatica L.

The current study was designed to assess the antinociceptive and skeleton muscle relaxant effect of leaves and barks of Buddleja asiatica in animal models. In acetic acid induced writhing test, pretreatment of ethanolic extract of leaves and barks evoked marked dose dependent antinociceptive effect with maximum of 70% and 67% pain relief at 300mg/kg i.p. respectively. In chimney test, the ethanolic extract of leaves and barks evoked maximum of 66.66% and 53.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In traction test, the ethanolic extract of leaves and barks caused maximum of 60% and 73.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In short, both leaves and barks demonstrated profound antinociceptive and skeleton muscle relaxant effects and thus the study provided natural healing agents for the treatment of said disorders.