Pharmacological and computational evaluation of fig for therapeutic potential in hyperactive gastrointestinal disorders

Abstract Background Ficus palmata (Fig), are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including inflammation, tumor, epilepsy, jaundice, influenza and bacillary dysentery. The present study aimed to evaluate the antidiarrheal, antisecretary, antispasmodic, antiulcer and anti motility properties of Ficus palmata. Methods In-vivo, in-vitro and in-silico techniques were used to investigate various gastrointestinal effects of Ficus palmata. Antidiarrheal, antisecretary, antispasmodic, antiulcer, anti motility and molecular docking were performed using castor oil induced diarrhea and fluid accumulation, isolated tissue preparations, ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina. Results Ficus palmata crude extract (Fp.Cr) exhibited protection against castor oil-induced diarrhea in mice and dose-dependently inhibited intestinal fluid secretions. Fp.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions in isolated rabbit jejunum preparations. It showed protective effect against gastric ulcers induced by ethanol-hydrochloric acid in rats. Fp.Cr reduced distance travelled by charcoal meal in the gastrointestinal transit model in mice. The plant constituents: psoralenoside and bergapten showed high binding affinities (E-value ≥ − 6.5 Kcal/mol) against histaminergic H1, calmodulin and voltage gated L-type calcium channels, while showed moderate affinities (E-value ≥7 Kcal/mol) against dopaminergic D2, adrenergic α1, muscranic M3, mu-opioid, whereas revealed lower affinities (E-value ≥9.5 Kcal/mol) vs. muscranic M1, histaminergic H2 and H+/K+ ATPase pump. Germanicol acetate and psoralene exhibited weak affinities against aforementioned targets. Conclusion This study reveals that Ficus palmata possesses anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility and anti-ulcer activities. The various constituents reveal different binding affinities against target proteins, which mediate the gastrointestinal functions.

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Antidiarrheal activity of methanolic leaf extract of Rumex vesicarius

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i1.24251 ◽

2016 ◽

Vol 11 (1) ◽

pp. 175 ◽

Cited By ~ 2

Author(s):

Imran Ahmad Khan ◽

Khalid Hussain Janbaz ◽

Fatima Saqib

Keyword(s):

Castor Oil ◽

Gastrointestinal Transit ◽

Intestinal Content ◽

Positive Control ◽

Tissue Preparation ◽

Rabbit Jejunum ◽

Antidiarrheal Activity ◽

Spontaneous Contractions

This study evaluates the antidiarrheal activity of Rumex vesicarius (leaf) by using in vitro and in vivo assays. Antidiarrheal effect of R. vesicarius was evaluated using castor oil-induced diarrhea model in rat. Weight and volume of the intestinal content were assessed using the enteropooling method. Atropine (3 mg/kg, i.p) was used as positive control. R. Vesicarius at the doses of 200 and 400 mg/kg p.o. significantly retarded castor oil-induced enteropooling and intestinal transit. The gastrointestinal transit rate was studied and R. vesicarius at the doses of 200 and 400 mg/kg significantly inhibited (p<0.001) weight and volume of intestinal content. R. vesicarius caused concentration-dependent (0.01–1 mg/mL) relaxation of spontaneous contractions in isolated rabbit jejunum tissue preparation and inhibited K+-80 induced contractions (0.01-5 mg/mL), similar to verapamil, suggestive of calcium channel blockade. Results obtained herein indicate that R. vesicarius may contain effective compounds which can be used as an antidiarrheal agent.

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Pharmacological Studies Pertaining to Smooth Muscle Relaxant, Platelet Aggregation Inhibitory and Hypotensive Effects of Ailanthus altissima

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1871696 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Hafiz Muhammad Abdur Rahman ◽

Muhammad Fawad Rasool ◽

Imran Imran

Keyword(s):

Smooth Muscle ◽

Platelet Aggregation ◽

Castor Oil ◽

Ailanthus Altissima ◽

Sd Rats ◽

High K ◽

Rabbit Jejunum ◽

Smooth Muscle Relaxant

Objective. This in vitro and in vivo study was conducted to rationalize some of traditional medicinal uses of Ailanthus altissima in gastrointestinal, respiratory, and cardiovascular systems. Materials. Crude extract of Ailanthus altissima (Aa.Cr) and its fractions were prepared and utilized in in vitro and in vivo studies. For in vitro studies, Aa.Cr was investigated on isolated rabbit jejunum, isolated tracheal strip, and isolated aorta of rat suspended in tissue organ bath. Platelet rich and platelet poor plasma were used to study platelet aggregation inhibitory activity. In vivo antidiarrheal effect of Aa.Cr was investigated on balb/c mice pretreated with castor oil to induce diarrhea and SD rats were used to study hypotensive activity. Results. Concentration dependent spasmolytic effects of Aa.Cr and its DCM fraction (Aa.DCM) were observed on spontaneous and spasmogen induced contractions in jejunum isolated from rabbit, but effect against high potassium (high-K+) induced contractions was more potent. Moreover Aa.Cr showed parallel shifting of calcium response curve to the right side. While its aqueous fraction (Aa.aq) caused spasmogenesis of isolated rabbit jejunum, this effect was blocked partially with prior administration of atropine (1μM). Concentration dependent protection against castor oil induced diarrhea was also observed. Relaxant effect was observed by the application of Aa.Cr and Aa.DCM against high-K+ and carbachol (CCh) induced contractions in tracheal strips isolated from SD rats, while Aa.Aq caused partial relaxation of high-K+ induced contractions, but no effect was observed against CCh induced contractions. Relaxation of rat aorta by the application of Aa.Cr and its fractions was also observed. Inhibition of force of contraction in rabbit atrium was also observed. Inhibition of platelet aggregation was observed against epinephrine and ADP induced aggregation. Conclusion. Keeping in view the observed results, it is concluded that smooth muscle relaxant, platelet aggregation inhibitory and hypotensive effect may be due to the blockage of calcium channels.

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Antispasmodic activity of Symplocos paniculata is mediated through opening of ATP-dependent K+ channel

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i2.24667 ◽

2016 ◽

Vol 11 (2) ◽

pp. 495 ◽

Cited By ~ 2

Author(s):

Khalid Hussain Janbaz ◽

Saba Akram ◽

Fatima Saqib ◽

Mamoona Khalid

Keyword(s):

Methanolic Extract ◽

Therapeutic Potential ◽

Scientific Basis ◽

K Channel ◽

Antispasmodic Activity ◽

Relaxant Effect ◽

Rabbit Jejunum ◽

Low K

Symplocos paniculata is a medicinal plant used by native healers to manage gastrointestinal ailments. The crude methanolic extract of S. paniculata was screened pharmacologically both in vitro and in vivo for the validation of its therapeutic potential. It suppressed the spontaneous activity of isolated rabbit jejunum preparations and also caused inhibition of the low K+ (20 mM)- induced spastic contractions in isolated rabbit jejunum preparations in a manner comparable to cromakalim. The relaxant effect was found to be blocked following glibenclamide exposure of the isolated tissue preparations similar to cromakalim, suggesting that observed response was likely to be mediated through opening of ATP dependent K+ channels. Following oral administration to mice provided protection against castor oil-induced diarrhea in a manner similar to loperamide. The plant material was found safe in toxicity study up to oral dose of 8 g/kg in mice. Hence, present study provides a scientific basis for the vernacular use of S. paniculata in gastro-intestinal system.

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Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110145151 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4626-4638 ◽

Cited By ~ 13

Author(s):

Reyhaneh Moradi-Marjaneh ◽

Seyed M. Hassanian ◽

Farzad Rahmani ◽

Seyed H. Aghaee-Bakhtiari ◽

Amir Avan ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Therapeutic Potential ◽

Vegf Signaling ◽

Anticancer Effects ◽

Inhibition Of Angiogenesis ◽

Underlying Mechanisms ◽

Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

Current Pharmaceutical Design ◽

10.2174/1381612826666200928160357 ◽

2020 ◽

Vol 26 ◽

Author(s):

Kondeti Ramudu Shanmugam ◽

Bhasha Shanmugam ◽

Gangigunta Venkatasubbaiah ◽

Sahukari Ravi ◽

Kesireddy Sathyavelu Reddy

Keyword(s):

Herbal Medicine ◽

Medicinal Plants ◽

Bioactive Compounds ◽

Diabetes Management ◽

Therapeutic Potential ◽

Public Health Problem ◽

In Vivo Studies ◽

Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

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GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties

Biology ◽

10.3390/biology10070610 ◽

2021 ◽

Vol 10 (7) ◽

pp. 610

Author(s):

Robin Park ◽

Andrew L. Coveler ◽

Ludimila Cavalcante ◽

Anwaar Saeed

Keyword(s):

Pancreatic Cancer ◽

Therapeutic Potential ◽

Glycogen Synthase ◽

Glycogen Synthase Kinase ◽

Glycogen Synthase Kinase 3 ◽

In Vivo Models ◽

Gsk 3Β ◽

Early Phase Clinical Trials

Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future.

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Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽

10.3390/pharmaceutics13040498 ◽

2021 ◽

Vol 13 (4) ◽

pp. 498

Author(s):

Mariaevelina Alfieri ◽

Antonietta Leone ◽

Alfredo Ambrosone

Keyword(s):

Therapeutic Potential ◽

Biological Activities ◽

Plant Biotechnology ◽

Bioactive Metabolites ◽

Anticancer Activities ◽

Long Distance ◽

In Vivo Models ◽

Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

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Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

Scientific Reports ◽

10.1038/s41598-020-79940-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Dalal ◽

Abdul Wahab Allaf ◽

Hind El-Zein

Keyword(s):

Theoretical Model ◽

Castor Oil ◽

In Vivo Studies ◽

Coating Materials ◽

Peg 400 ◽

The Mean ◽

Usp Apparatus ◽

Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

International Journal of Molecular Sciences ◽

10.3390/ijms22157920 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7920

Author(s):

Myroslava Mytsyk ◽

Giulia Cerino ◽

Gregory Reid ◽

Laia Gili Sole ◽

Friedrich S. Eckstein ◽

...

Keyword(s):

Adipose Tissue ◽

Therapeutic Potential ◽

Stromal Vascular Fraction ◽

Human Adipose Tissue ◽

Bioreactor Culture ◽

Proliferating Cells ◽

Angiogenic Potential ◽

Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

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Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽

10.3390/molecules26103005 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3005

Author(s):

Kanchan Bhardwaj ◽

Ana Sanches Silva ◽

Maria Atanassova ◽

Rohit Sharma ◽

Eugenie Nepovimova ◽

...

Keyword(s):

Experimental Data ◽

Potential Role ◽

Therapeutic Potential ◽

Fungal Infections ◽

Cell Damage ◽

Cancer Growth ◽

Naturally Occurring ◽

Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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