Publications by authors named "Azhar Rasul"

97 Publications

Dietary biomolecules as promising regenerative agents for peripheral nerve injury: An emerging nutraceutical-based therapeutic approach.

J Food Biochem 2021 Oct 31:e13989. Epub 2021 Oct 31.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.

Peripheral nerve damage is a debilitating condition that can result in partial or complete functional loss as a result of axonal degeneration, as well as lifelong dependence. Many therapies have been imbued with a plethora of positive features while posing little risks. It is worth noting that these biomolecules work by activating several intrinsic pathways that are known to be important in peripheral nerve regeneration. Although the underlying mechanism is used for accurate and speedy functional recovery, none of them are without side effects. As a result, it is believed that effective therapy is currently lacking. The dietary biomolecules-based intervention, among other ways, is appealing, safe, and effective. Upregulation of transcription factors, neurotrophic factors, and growth factors such as NGF, GDNF, BDNF, and CTNF may occur as a result of these substances' dietary intake. Upregulation of the signaling pathways ERK, JNK, p38, and PKA has also been seen, which aids in axonal regeneration. Although several mechanistic approaches to understanding their involvement have been suggested, more work is needed to reveal the amazing properties of these biomolecules. We have discussed in this article that how different dietary biomolecules can help with functional recovery and regeneration after an injury. PRACTICAL APPLICATIONS: Based on the information known to date, we may conclude that treatment techniques for peripheral nerve injury have downsides, such as complications, donor shortages, adverse effects, unaffordability, and a lack of precision in efficacy. These difficulties cast doubt on their efficacy and raise severe concerns about the prescription. In this situation, the need for safe and effective therapeutic techniques is unavoidable, and dietary biomolecules appear to be a safe, cost-efficient, and effective way to promote nerve regeneration following an injury. The information on these biomolecules has been summarized here. Upregulation of transcription factors, neurotrophic factors, and growth factors, such as NGF, GDNF, BDNF, and CTNF, as well as the ERK, JNK, p38, and PKA, signaling pathways, may stimulate axonal regeneration.
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http://dx.doi.org/10.1111/jfbc.13989DOI Listing
October 2021

In-vitro cytotoxic evaluation of newly designed ciprofloxacin-oxadiazole hybrids against human liver tumor cell line (Huh7).

Pak J Pharm Sci 2021 May;34(3(Supplementary)):1143-1148

Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan.

Fluoroquinolones are targets of interest due to their broad spectrum antibacterial activity. Structure-activity relationship (SAR) of fluoroquinolones clearly indicates that substitution at C-7 position enhances the lipophilicity of these scaffolds resultantly affording pharmacologically significant compounds. Therefore, various ciprofloxacin-oxadiazole hybrids were synthesized and characterized by spectral analysis. Cytotoxic activity of these derivatives was assessed using human liver tumor cells (Huh7). One dose anticancer test results revealed moderate cytotoxicity of the newly synthesized compounds against this cell line. As the only compound 4a depicted comparatively lower cell viability value (81.91% using 100μg/mL concentration) than the other compounds.
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May 2021

Synthetic molecules targeting yes associated protein activity as chemotherapeutics against cancer.

Chem Biol Drug Des 2021 Dec 3;98(6):1025-1037. Epub 2021 Oct 3.

Fujian Provincial Key Laboratory of Reproduction Health Research, School of Medicine, Xiamen University, Xiamen, China.

The Hippo signaling pathway extorts several signals that concomitantly target the activity of transcriptional cofactor yes associated protein (YAP). YAP is a key regulator that elicits signature gene expression by coupling with transcriptional enhanced associate domain (TEAD) family of transcriptional factors. The YAP-TEAD complex via target gene expression gets associated with the development, proliferation, and progression of cancerous cells. Moreover, YAP adorns cells with several oncogenic traits such as inhibition of apoptosis, enhanced proliferation, drug resistance, and immune response suppression, which later became associated with various diseases, particularly cancer. Therefore, inhibition of the YAP activity is an appealing and viable therapeutic target for cancer treatment. This review highlights the recent advances in existing and novel synthetic therapeutics targeting YAP inhibition and regulation. The synthetically produced YAP belonging to cyclic peptides and DC-TEADin02 and vinyl sulfonamide class of compounds are the most potent compounds to inhibit the YAP-TEAD expression by targeting protein-protein interaction (IC  = 25 nM) and palmitate binding central pocket of TEAD (IC  = 197 nM), respectively. On the other hand, Chlorpromazine belonging to phenothiazines class has the least potential to suppress YAP via proteasomal degradation (cell viability value of <20% at 40 µM).
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http://dx.doi.org/10.1111/cbdd.13960DOI Listing
December 2021

Nickel nanoparticles induce hepatotoxicity via oxidative and nitrative stress-mediated apoptosis and inflammation.

Toxicol Ind Health 2021 Oct 25;37(10):619-634. Epub 2021 Sep 25.

Department of Analytical Chemistry and Instrumental Analysis, Institute of Sport- National Research Institute, Warsaw, Poland.

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kβ indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1β, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.
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http://dx.doi.org/10.1177/07482337211034711DOI Listing
October 2021

Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy.

Birth Defects Res 2021 Nov 22;113(19):1407-1421. Epub 2021 Sep 22.

Department of Pharmacology, Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.

Objectives: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy.

Methods: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out.

Results: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001-.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01-.001) alteration of lipid profile in the pregnant than the nonpregnant animals.

Conclusion: Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.
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http://dx.doi.org/10.1002/bdr2.1957DOI Listing
November 2021

(leaves) supplementation exerts curative effects on promoting functional recovery in a mouse model of peripheral nerve injury.

Food Sci Nutr 2021 Sep 9;9(9):5016-5027. Epub 2021 Jul 9.

Institute of Nutrition and Food Science University of Dhaka Dhaka Bangladesh.

Peripheral nerve injuries are among those complicated medical conditions, which are still waiting for their highly effective first-line therapies. In this study, the role of crude leaves was evaluated at different doses for their effectiveness in improving functional recovery following sciatic nerve injury-induced in the mouse model. Thirty-two healthy albino mice were divided into four groups as Normal chow group (control,  = 8) and chow groups (50 mg/kg ( = 8), 100 mg/kg ( = 8) and 200 mg/kg ( = 8)). Behavioral analyses were performed to assess and compare improved functional recovery along with skeletal muscle mass measurement in all groups. Serum samples were analyzed for oxidative stress markers. Results showed that leaves at dose-dependent manner showed statistically prominent ( < .05) increase in sensorimotor functions reclamation as confirmed by behavioral analyses along with muscle mass restoration and prominent decline in TOS and momentous increase in TAC along with the augmented activity of antioxidative enzymes.
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http://dx.doi.org/10.1002/fsn3.2455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441272PMC
September 2021

Combination of natural antivirals and potent immune invigorators: A natural remedy to combat COVID-19.

Phytother Res 2021 Aug 15. Epub 2021 Aug 15.

Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Al-Beheira, Egypt.

The flare-up in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in December 2019 in Wuhan, China, and spread expeditiously worldwide has become a health challenge globally. The rapid transmission, absence of anti-SARS-CoV-2 drugs, and inexistence of vaccine are further exacerbating the situation. Several drugs, including chloroquine, remdesivir, and favipiravir, are presently undergoing clinical investigation to further scrutinize their effectiveness and validity in the management of COVID-19. Natural products (NPs) in general, and plants constituents specifically, are unique sources for various effective and novel drugs. Immunostimulants, including vitamins, iron, zinc, chrysin, caffeic acid, and gallic acid, act as potent weapons against COVID-19 by reinvigorating the defensive mechanisms of the immune system. Immunity boosters prevent COVID-19 by stimulating the proliferation of T-cells, B-cells, and neutrophils, neutralizing the free radicals, inhibiting the immunosuppressive agents, and promoting cytokine production. Presently, antiviral therapy includes several lead compounds, such as baicalin, glycyrrhizin, theaflavin, and herbacetin, all of which seem to act against SARS-CoV-2 via particular targets, such as blocking virus entry, attachment to host cell receptor, inhibiting viral replication, and assembly and release.
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http://dx.doi.org/10.1002/ptr.7228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441799PMC
August 2021

A review on phyto-pharmacology of Oxalis corniculata.

Comb Chem High Throughput Screen 2021 Aug 13. Epub 2021 Aug 13.

Department of Chemistry, Faculty of Science, Cankiri Karatekin University, 18100 Cankiri, Turkey.

Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, phlobatannins along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, anti-bacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess potential for the cure of various diseases, however, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.
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http://dx.doi.org/10.2174/1386207324666210813121431DOI Listing
August 2021

Synthesis and anticancer evaluation of 2-oxo-2-(arylamino) ethyl 4-phenylpiperazine-1-carbodithioates.

Pak J Pharm Sci 2021 Jan;34(1(Supplementary)):353-357

Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan.

Piperazine moiety is found as an efficient pharmacological scaffold in various drugs. To explore the anticancer potential of piperazine framework, a series of novel N-acetamides derivatives of phenyl piperazine containing di-thio-carbamate moiety was designed and synthesized. HNMR, CNMR, FT-IR and mass spectrometry were used for the structures elucidation of these derivatives. In-vitro cytotoxic evaluation of the prepared novel compounds against lung carcinoma A-549 was carried out using standard MTT assay. All the di-thio-carbamate-piperazine derivatives exhibited moderate to excellent cytotoxic potential against A-549 cell line based on cell viability. Particularly, 6e was found to be the most potent derivative with cell viability 34.12±0.73 % at 100 μg/mL concentration and represents promising lead compound for future progress.
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January 2021

Protective effect of Heliotropium strigosum 70% aqueous methanolic extract against paracetamol induced hepatotoxicity in mice.

Pak J Pharm Sci 2021 Mar;34(2(Supplementary)):693-698

Cadson College of Pharmacy, University of the Punjab, Khariaan Campus, Lahore, Pakistan.

The study was carried out to evaluate the hepatoprotective potential of aqueous methanolic extract of Heliotropium strigosum (HSME) against paracetamol induced hepatotoxicity in Swiss albino mice. The plant powder (1.5Kg) was macerated in aqueous methanol (30:70) for 7 days. The extract was evaluated for the presence of different phytochemicals and High-performance liquid chromatography (HPLC) analysis. HSME was orally administered to mice at 125, 250 and 500mg/kg for 8 days followed by paracetamol intoxication (500mg/kg orally) on the 8th day using silymarin as standard control. All the therapy was administered by oral gavage. The liver biochemical parameters and histopathological evaluation were carried out to assess changes in liver function and histology. HPLC analysis confirmed the presence of quercetin, kaempferol, and other phenolic compounds. Treatment with the extract resulted in notable (p<0.05) reduction in liver parameters in dose dependent manner. The action of HSME 500mg/kg dose was comparable to silymarin. The effect of HSME against paracetamol induced hepatotoxicity was demonstrated by protective changes in the liver histopathological which proved the traditional uses of the plant.
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March 2021

In silico-based identification of phytochemicals as novel human phosphoglycerate mutase 1 (PGAM1) inhibitors for cancer therapy.

Pak J Pharm Sci 2021 Mar;34(2(Supplementary)):665-670

Department of Zoology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

Targeting cancer-specific metabolic and mitochondrial remodeling has emerged as a novel and selective strategy for cancer therapy during recent years. Phosphoglycerate Mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate and plays a critical role in cancer progression by coordinating glycolysis and biosynthesis. PGAM1 has been reported to be over expressed in a variety of cancer types and its inhibition results in decreased tumor growth and metastasis. Recently, there has been a growing interest in identification and characterization of novel PGAM1 inhibitors for the treatment of cancer. In the current study, in silico tools were used to find out natural inhibitors of PGAM1. For docking studies, a database of 5006 phytochemicals were docked against PGAM1, using MOE software in order to identify the compounds which show better binding affinities than PGMI-004A. Out of 5006 compounds screened, eight compounds (1,3-cyclopentanedione, glyflavanone B, 6-demethoxytangeretin, gnaphaliin, lantalucratin A and -(-) morelensin, abyssinin II and monotesone-A) showed significant binding affinity with PGAMI active site. Further, the eight selected compounds were evaluated for different pharmacokinetics parameters using admetSAR, the obtained results demonstrated that none of these hit compounds violated Lipinski's drug rule of 5 and all the hit compounds possess favorable ADMET properties. This study has unveiled the potential of phytochemicals that could serve as probable lead candidates for the development of PGAM1 inhibitors as anti-cancer agents.
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March 2021

Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Biomed Res Int 2021 26;2021:5514669. Epub 2021 May 26.

The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University (NENU), Changchun, China.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts (leaf, seed, and bark) and bark extracts were found to be inhibitors of PKM2. In the current study, (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 g/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC values. (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC values of 108 g/ml and 33 g/ml, respectively. Literature-based phytochemical analysis of was carried out, and -derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via biochemical assay. The results of this study provide novel findings for possible mechanism of action of (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that might be of therapeutic interest for the treatment of TNBC.
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http://dx.doi.org/10.1155/2021/5514669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175167PMC
October 2021

Synthesis, Hemolytic Studies, and Modeling of Novel Acefylline-1,2,4-Triazole Hybrids as Potential Anti-cancer Agents against MCF-7 and A549.

ACS Omega 2021 May 30;6(18):11943-11953. Epub 2021 Apr 30.

Department of Pharmacology, Government College University Faisalabad, Faisalabad 38000, Pakistan.

A series of novel theophylline-7-acetic acid (acefylline)-derived 1,2,4-triazole hybrids with -phenyl acetamide moieties (-) have been synthesized and tested for their inhibitory () potential against two cancer cell lines, A549 (lung) and MCF-7 (breast), using MTT assay. Among these derivatives, , , , , and displayed remarkable activity against both cancer cell lines having cell viability values in the 21.74 ± 1.60-55.37 ± 4.60% range compared to acefylline (86.32 ± 1.75%) using 100 μg/μL concentration of compounds. These compounds were further screened against the A549 cancer cell line (lung) to find their half-maximal inhibitory concentration (IC) by applying various concentrations of these compounds. Compound (2-(5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1-purin-7(6)-yl)methyl)-4-phenyl-4-1,2,4-triazol-3-ylthio)---tolylacetamide) with the least IC value (1.25 ± 1.36 μM) was discerned as a strong inhibitor of cancer cell multiplication in both cell lines (A549 and MCF-7). Their hemolytic studies revealed that all of them had very low cytotoxicity. Finally, modeling was carried out to find the mode of binding of the highly active compound (), which was according to the results of anti-cancer activity.
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http://dx.doi.org/10.1021/acsomega.1c00424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154016PMC
May 2021

Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance.

Clin Epigenetics 2021 05 29;13(1):120. Epub 2021 May 29.

Department of Biotechnology, Abdul Wali Khan University Mardan (AWKUM), Mardan, 23200, Pakistan.

At present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.
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http://dx.doi.org/10.1186/s13148-021-01107-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164819PMC
May 2021

Radioprotective Role of Natural Polyphenols: From Sources to Mechanisms.

Anticancer Agents Med Chem 2021 Apr 18. Epub 2021 Apr 18.

Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000. Pakistan.

The identification and development of radioprotective agents has emerged as a subject matter of research during recent years due to the growing usage of ionizing radiation in different areas of human life. Previous work on synthetic radioprotectors has achieved limited progress because of the numerous issues associated with toxicity. Compounds extracted from plants have potential to serve as lead candidates for developing ideal radioprotectors due to their low cost, safety and selectivity. Polyphenols are the most abundant and commonly dispersed group of biologically active molecules possessing broad range of pharmacological activities. Polyphenols have displayed efficacy for radioprotection during various investigations and can be administered at high doses with lesser toxicity. Detoxification of free radicals, modulating inflammatory responses, DNA repair, stimulation of hematopoietic recovery, and immune functions are the main mechanisms for radiation protection with polyphenols. Epicatechin, epigallocatechin-3-gallate, apigenin, caffeic acid phenylethylester, and silibinin provide cytoprotection together with the suppression of many pro-inflammatory cytokines owing to their free radical scavenging, anti-oxidant, and anti-inflammatory properties. Curcumin, resveratrol, quercetin, gallic acid, and rutin's radioprotective properties are regulated primarily by direct or indirect decline in cellular stress. Thus, polyphenols may serve as potential candidates for radioprotection in the near future, however, extensive investigations are still required to better understand their protection mechanisms.
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http://dx.doi.org/10.2174/1871520621666210419095829DOI Listing
April 2021

Chalepin and Chalepensin: Occurrence, Biosynthesis and Therapeutic Potential.

Molecules 2021 Mar 14;26(6). Epub 2021 Mar 14.

Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, UK.

Dihydrofuranocoumarin, chalepin () and furanocoumarin, chalepensin () are 3-prenylated bioactive coumarins, first isolated from the well-known medicinal plant L. (Fam: Rutaceae) but also distributed in various species of the genera , and . The distribution of these compounds appears to be restricted to the plants of the family Rutaceae. To date, there have been a considerable number of bioactivity studies performed on coumarins and , which include their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral and calcium antagonistic properties. This review article presents a critical appraisal of publications on bioactivity of these 3-prenylated coumarins in the light of their feasibility as novel therapeutic agents and investigate their natural distribution in the plant kingdom, as well as a plausible biosynthetic route.
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http://dx.doi.org/10.3390/molecules26061609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999183PMC
March 2021

Radioprotective Potential of Nutraceuticals and their Underlying Mechanism of Action.

Anticancer Agents Med Chem 2021 Feb 22. Epub 2021 Feb 22.

Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Enseñanza e Investigación en Bacteriología Alimentaria (CLEIBA), Universidad Nacional Mayor de San Marcos, Lima15001. Peru.

Radiations are an efficient treatment modality in cancer therapy. Besides the treatment effects of radiations, the ionizing radiations interact with biological systems and generate reactive oxygen species that interfere with the normal cellular process. Previous investigations of synthetic radioprotectors have shown less effectiveness, mainly owing to some limiting effects. The nutraceuticals act as efficient radioprotectors to protect the tissues from the deleterious effects of radiation. The main radioprotection mechanism of nutraceuticals is the scavenging of free radicals while other strategies are involved modulation of signaling transduction of pathways like MAPK (JNK, ERK1/2, ERK5, and P38), NF-kB, cytokines, and their protein regulatory genes expression. The current review is focused on the radioprotective effects of nutraceuticals including vitamin E, -C, organosulphur compounds, phenylpropanoids, and polysaccharides. These natural entities protect against radiation-induced DNA damage. The review mainly entails the antioxidant perspective and mechanism of action of their radioprotective activities on a molecular level, DNA repair pathway, anti-inflammation, immunomodulatory effects, the effect on cellular signaling pathways, and regeneration of hematopoietic cells.
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http://dx.doi.org/10.2174/1871520621666210223101246DOI Listing
February 2021

Methanolic extract of Fennel () escalates functional restoration following a compression injury to the sciatic nerve in a mouse model.

Food Sci Nutr 2021 Feb 13;9(2):701-710. Epub 2020 Dec 13.

Institute of Nutrition and Food Science University of Dhaka Dhaka Bangladesh.

Peripheral nerve injury (PNI) is one of the major health concerns faced by the community at present. Till now, available therapeutic approaches are ineffective to fully heal a nerve injury and to assure the functional recovery entirely. Natural compounds can prove attractive and effective drug candidates to bridge up this gap. In this scenario, the present study was designed to explore the role of methanolic extract of () seeds in accelerating the function regain following a sciatic nerve injury in a mouse model. For this purpose, 12 adult healthy albino mice (BALB/C), 8-10 weeks old, were grouped as control (Ctrl,  = 6) and treatment (Trt,  = 6). The treated group was given methanolic extract of F. vulgare (200 mg/kg per day) started from the day of nerve crush until the end of the study. The sensorimotor function regain assessed by hot plate test, grip strength, and SFI assessments was found significantly ( < .05) ameliorated in the treated group. A prominent improvement in the muscle mass of the treated group further affirmed these effects. Furthermore, morphometric analysis of muscle fiber cross-sectional area of tibialis anterior muscle between groups revealed a noticeable improvement in muscle fibers' diameter of the treated group. Conclusively, these findings suggest that methanolic extract exhibits the potential to escalate functional recovery following a peripheral nerve injury. However, the real players of this extract and the mechanism involved in boosting functional restoration need to be dissected by further work.
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http://dx.doi.org/10.1002/fsn3.2033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866564PMC
February 2021

Furanodiene: A Novel, Potent, and Multitarget Cancer-fighting Terpenoid.

Curr Pharm Des 2021;27(22):2628-2634

Department of Chemistry, Faculty of Science, Cankiri Karatekin University, 18100 Cankiri, Turkey.

Natural products have served as a limitless reservoir of bioactive scaffolds for drug discovery against several disorders. Furanodiene is a bioactive natural product isolated from several plants of genus Curcuma. Its therapeutic potential against cancer, inflammation, and angiogenesis has been well-documented. The current review is an update about the natural sources and anti-cancer action mechanism of furanodiene. Furanodiene exerts its anti-cancer effects via induction of apoptosis in several cancer types by modulating MAPKs/ERK, NF-κB, and Akt pathways. Furanodiene has been systematically studied for its anti-cancer potential. However, pharmacokinetics, pharmacodynamics, pre-clinical and clinical studies still needed to be conducted to completely validate the potential of furanodiene for the treatment of cancer.
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http://dx.doi.org/10.2174/1381612827666210211125304DOI Listing
October 2021

Appraisal of Anti-Arthritic and Anti-Inflammatory Potential of Folkloric Medicinal Plant Peganum Harmala.

Endocr Metab Immune Disord Drug Targets 2021 Feb 8. Epub 2021 Feb 8.

Department of Zoology, Government College University Faisalabad, Faisalabad, . Pakistan.

Background: Peganum harmala is traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods.

Methods: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days.

Results: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 µg/ml respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats.

Conclusion: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities which primarily might be attributed to alkaloids, flavonoids and phenols.
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http://dx.doi.org/10.2174/1871530321666210208211310DOI Listing
February 2021

Retrospective study of frequency of ABO and Rhesus blood group among population of Safdarabad and Faisalabad cities of Pakistan.

BMC Res Notes 2021 Jan 7;14(1):12. Epub 2021 Jan 7.

Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.

Objective: The current study aimed to investigate the ABO and rhesus (Rh) blood group frequency in the people of District Faisalabad and Sheikhupura, Punjab Province, Pakistan. The retrospective study was conducted on more than thirty thousand people including both male and female patients admitted to the Tehsil Headquarter Hospital, Safdarabad and The Best Hospital, Faisalabad. Blood samples were taken from each subject and subsequently ABO and Rh blood groups were evaluated separately. The antigen antibody agglutination slide test for blood grouping (ABO) and Rh were used to assess the blood group frequencies.

Results: The frequencies of ABO blood group distribution indicated that blood group B was predominant in the people of Safdarabad followed by O, A and AB respectively. While, among people of Faisalabad, blood group O was predominant followed B, A and AB respectively. Rh negative phenotype was found lesser distributed as compared to the positive Rh phenotype.
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http://dx.doi.org/10.1186/s13104-020-05429-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792172PMC
January 2021

Chemical characterization and anti-arthritic appraisal of Monotheca buxifolia methanolic extract in Complete Freund's Adjuvant-induced arthritis in Wistar rats.

Inflammopharmacology 2021 Apr 2;29(2):393-408. Epub 2021 Jan 2.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

The current study was designed to evaluate the anti-oxidant and anti-arthritic potential of a traditionally used herb, Monotheca buxifolia. The M. buxifolia methanolic extract (MBME) was prepared from the aerial parts of the plant followed by chemical characterization with GC-MS. The anti-oxidant potential of the MBME was demonstrated by DPPH scavenging activity. The effects of MBME on protein denaturation and membrane stabilization were determined by inhibition of egg albumin denaturation and RBC membrane stabilization assays, respectively. The in vivo anti-arthritic potential of the MBME at 50, 100, and 150 mg/kg/day was evaluated in Complete Freund's Adjuvant-induced polyarthritis in Wistar rats treated for 21 days. Phytochemicals, such as linolenic acid methyl ester, n-hexadecanoic acid, vitamin E, α-amyrin, and β-amyrin were detected in the GC-MS analysis. The plant extract exhibited a 55.20 ± 0.69% scavenging of free radicals at 100 µg/ml concentration. It significantly (p < 0.05) stabilized human RBC membrane (65.06 ± 0.22%) and inhibited protein denaturation (70.53 ± 0.34%) at 100 mg/ml concentration. The diclofenac sodium (DS) and MBME at 150,100, and 50 mg/kg reduced the paw edema, restored the body weight, and altered blood parameters including CRP. The MBME significantly reduced the MDA and increased the SOD, CAT, and GSH levels in liver tissue homogenate in treated rats. The serum concentration of TNF-α and PGE2 was remarkably (p < 0.01-< 0.0001) restored by the DS and MBME dose dependently. The histopathological study showed that MBME 150 mg/kg commendably restored the ankle joint inflammation, bone erosion, and cartilage damage in polyarthritic rats. It was concluded that the anti-oxidant, anti-inflammatory and anti-arthritic effects of MBME might be attributed to phenols, flavonoids, triterpenoids, vitamin E, phytol, and other fatty acids. This study showed the anti-arthritic potential of Monotheca buxifolia and thus validates its traditional claim.
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http://dx.doi.org/10.1007/s10787-020-00783-7DOI Listing
April 2021

Corrigendum to "Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells".

Evid Based Complement Alternat Med 2020 8;2020:7939705. Epub 2020 Oct 8.

Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, China.

[This corrects the article DOI: 10.1155/2012/957568.].
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http://dx.doi.org/10.1155/2020/7939705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732371PMC
October 2020

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential.

Curr Pharm Des 2021 ;27(34):3591-3601

Department of Physiology and Biochemistry, University of Malta, Msida, MSD2080, Malta.

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD.
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http://dx.doi.org/10.2174/1381612826666201112144006DOI Listing
November 2021

Physcion and Physcion 8-O-β-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities.

Curr Drug Targets 2021 ;22(5):488-504

School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, England, United Kingdom.

Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.
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http://dx.doi.org/10.2174/1389450121999201013154542DOI Listing
November 2021

Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19.

Phytomedicine 2021 May 22;85:153310. Epub 2020 Aug 22.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, 12613, Egypt.

Background: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic.

Purpose: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation.

Methods: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions.

Results: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 M, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes.

Conclusion: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.
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http://dx.doi.org/10.1016/j.phymed.2020.153310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442560PMC
May 2021

Lam.ameliorates the muscles function recovery following an induced insult to the Sciatic nerve in a mouse model.

Food Sci Nutr 2020 Aug 11;8(8):4009-4016. Epub 2020 Jul 11.

University of Gambia Serrekunda Gambia.

Peripheral nerve injury (PNI) is an incapacitating situation and has no effective therapy until now. We examined the possible role of crude leaves of Lam. at 200 mg/kg body weight in accelerating the functional regain in the sciatic nerve lesion induced mouse model (Adult male albino mice (BALB/c). Motor functions were evaluated by using the sciatic functional index, muscle mass, and muscle grip strength measurement, whereas the sensory functions were evaluated by using the hot plate test. Blood glucose levels and blood cell composition were also analyzed. We found that the crude leaves endorse the sensory and motor functions reclamation following the PNI with a statistically significant difference ( < .05). It also revitalizes the gastrocnemius muscle by mass restoration with glycemic management perspective. Conclusively, the crude powder of leaves exhibited a function restoration boosting property and further detailed studies for its application as a therapeutic agent are strongly recommended.
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http://dx.doi.org/10.1002/fsn3.1620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455924PMC
August 2020

Synthesis, characterization and antimicrobial activity of norfloxacin based acetohydrazides.

Pak J Pharm Sci 2020 Mar;33(2(Supplementary)):855-860

Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.

The drug resistance phenomenon in microbes is resulting in the ineffectiveness of available drugs to treat the infections. Thus, there is a continued need to discover new molecules to combat the drug resistance phenomenon. Norfloxacin is a fluoroquinolone antibiotic that is used for the treatment of urinary tract infections. In this research work, norfloxacin is structurally modified by hybridizing with a range of substituted acetohydrazidic moieties through a multistep reaction. The first step involves the coupling of norfloxacin 1 with methyl chloroacetate followed by the treatment with hydrazine hydrate to result in corresponding acetohydrazide 3. A range of substituted benzaldehydes were reacted with the acetohydrazide to form the targeted series of norfloxacin derivatives 4a-i. The final compounds were screened for antimicrobial activity. Among the tested compounds, 4c, 4d, 4e and 4f displayed better antifungal activity against F.avenaceum, while compound 4c and 4e were active against F. bubigeum.
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March 2020

Anticancer natural medicines: An overview of cell signaling and other targets of anticancer phytochemicals.

Eur J Pharmacol 2020 Dec 14;888:173488. Epub 2020 Aug 14.

Department of Zoology, College of Science, King Saud University, 2455, Riyadh, 11451, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.

Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor β pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.
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http://dx.doi.org/10.1016/j.ejphar.2020.173488DOI Listing
December 2020

Ginkgetin: A natural biflavone with versatile pharmacological activities.

Food Chem Toxicol 2020 Nov 9;145:111642. Epub 2020 Aug 9.

Department of Medical Biology, Faculty of Medicine, Nigde Ömer Halisdemir University, Nigde Campus, 51240, Turkey.

Natural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-κB, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro-hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neurodegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.
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http://dx.doi.org/10.1016/j.fct.2020.111642DOI Listing
November 2020
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