An overview of anti-SARS-CoV-2 and anti-inflammatory potential of baicalein and its metabolite baicalin: Insights into molecular mechanisms.

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is highly contagious infection that breaks the healthcare systems of several countries worldwide. Till to date, no effective antiviral drugs against COVID-19 infection have reached the market, and some repurposed drugs and vaccines are prescribed for the treatment and prevention of this disease. The currently prescribed COVID-19 vaccines are less effective against the newly emergent variants of concern of SARS-CoV-2 due to several mutations in viral spike protein and obviously there is an urgency to develop new antiviral drugs against this disease. In this review article, we systematically discussed the anti-SARS-CoV-2 and anti-inflammatory efficacy of two flavonoids, baicalein and its 7-O-glucuronide, baicalin, isolated from Scutellaria baicalensis, Oroxylum indicum, and other plants as well as their pharmacokinetics and oral bioavailability, for development of safe and effective drugs for COVID-19 treatment. Both baicalein and baicalin target the activities of viral S-, 3CL-, PL-, RdRp- and nsp13-proteins, and host mitochondrial OXPHOS for suppression of viral infection. Moreover, these compounds prevent sepsis-related inflammation and organ injury by modulation of host innate immune responses. Several nanoformulated and inclusion complexes of baicalein and baicalin have been reported to increase oral bioavailability, but their safety and efficacy in SARS-CoV-2-infected transgenic animals are not yet evaluated. Future studies on these compounds are required for use in clinical trials of COVID-19 patients.

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III.

Despite recent advances in single-molecule and structural analysis of condensin activity in vitro, mechanisms of functional condensin loading and loop extrusion that lead to specific chromosomal organization remain unclear. In Saccharomyces cerevisiae, the most prominent condensin loading site is the rDNA locus on chromosome XII, but its repetitiveness deters rigorous analysis of individual genes. An equally prominent non-rDNA condensin site is located on chromosome III (chrIII). It lies in the promoter of a putative non-coding RNA gene called RDT1, which is in a segment of the recombination enhancer (RE) that dictates MATa-specific chrIII organization. Here, we unexpectedly find that condensin is recruited to the RDT1 promoter in MATa cells through hierarchical interactions with Fob1, Tof2, and cohibin (Lrs4/Csm1), a set of nucleolar factors that also recruit condensin to the rDNA. Fob1 directly binds to this locus in vitro, while its binding in vivo depends on an adjacent Mcm1/α2 binding site that provides MATa cell specificity. We also uncover evidence for condensin-driven loop extrusion anchored by Fob1 and cohibin at RDT1 that unidirectionally extends toward MATa on the right arm of chrIII, supporting donor preference during mating-type switching. S. cerevisiae chrIII therefore provides a new platform for the study of programmed condensin-mediated chromosome conformation.

Therapeutic potential of green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG) in SARS-CoV-2 infection: Major interactions with host/virus proteases.

Background: The current COVID-19 pandemic from the human pathogenic virus SARS-CoV-2 has resulted in a major health hazard globally. The morbidity and transmission modality of this disease are severe and uncontrollable. As no effective clinical drugs are available for treatment of COVID-19 infection till to date and only vaccination is used as prophylaxis and its efficacy is restricted due to emergent of new variants of SARS-CoV-2, there is an urgent need for effective drugs for its treatment. Purpose: The aim of this review was to provide a detailed analysis of anti-SARS-CoV-2 efficacy of (-)-epigallocatechin-3-O-gallate (EGCG), a major catechin constituent of green tea (Camellia sinensis (L.) Kuntze) beverage to highlight the scope of EGCG in clinical medicine as both prophylaxis and treatment of present COVID-19 infection. In addition, the factors related to poor oral bioavailabilty of EGCG was also analysed for a suggestion for future research in this direction. Study design: We collected the published articles related to anti-SARS-CoV-2 activity of EGCG against the original strain (Wuhan type) and its newly emerged variants of SARS-CoV-2 virus. Methods: A systematic search on the published literature was conducted in various databases including Google Scholar, PubMed, Science Direct and Scopus to collect the relevant literature. Results: The findings of this search demonstrate that EGCG shows potent antiviral activity against SARS-CoV-2 virus by preventing viral entry and replication in host cells in vitro models. The studies on the molecular mechanisms of EGCG in inhibition of SARS-CoV-2 infection in host cells reveal that EGCG blocks the entry of the virus particles by interaction with the receptor binding domain (RBD) of viral spike (S) protein to host cell surface receptor protease angiotensin-converting enzyme 2 (ACE2) as well as suppression of the expressions of host proteases, ACE2, TMPRSS2 and GRP78, required for viral entry, by Nrf2 activation in host cells. Moreover, EGCG inhibits the activities of SARS-CoV-2 main protease (Mpro), papain-like protease (PLpro), endoribonuclease Nsp15 in vitro models and of RNA-dependent RNA polymerase (RdRp) in molecular docking model for suppression of viral replication. In addition, EGCG significantly inhibits viral inflammatory cytokine production by stimulating Nrf2- dependent host immune response in virus-infected cells. EGCG significantly reduces the elevated levels of HMGB1, a biomarker of sepsis, lung fibrosis and thrombotic complications in viral infections. EGCG potentially inhibits the infection of original (Wuhan type) strain of SARS-CoV-2 and other newly emerged variants as well as the infections of SARS-CoV-2 virus spike-protein of WT and its mutants-mediated pseudotyped viruses . EGCG shows maximum inhibitory effect against SARS-CoV-2 infection when the host cells are pre-incubated with the drug prior to viral infection. A sorbitol/lecithin-based throat spray containing concentrated green tea extract rich in EGCG content significantly reduces SARS-CoV-2 infectivity in oral mucosa. Several factors including degradation in gastrointestinal environment, low absorption in small intestine and extensive metabolism of EGCG are responsible for its poor bioavailability in humans. Pharmacokinetic and metabolism studies of EGCG in humans reveal poor bioavailability of EGCG in human plasma and EGCG-4"-sulfate is its major metabolite. The concentration of EGCG-4"-sulfate in human plasma is almost equivalent to that of free EGCG (Cmax 177.9 vs 233.5 nmol/L). These findings suggest that inhibition of sulfation of EGCG is a crucial factor for improvement of its bioavailability. In vitro study on the mechanism of EGCG sulfonation indicates that sulfotransferases, SULT1A1 and SULT1A3 are responsible for sulfonation in human liver and small intestine, respectively. Some attempts including structural modifications, and nanoformulations of EGCG and addition of nutrients with EGCG have been made to improve the bioavailability of EGCG. Conclusions: The findings of this study suggest that EGCG has strong antiviral activity against SARS-CoV-2 infection independent of viral strains (Wuhan type (WT), other variants) by inhibition of viral entry and replication in host cells in vitro models. EGCG may be useful in reduction of this viral load in salivary glands of COVID-19 patients, if it is applied in mouth and throat wash formulations in optimal concentrations. EGCG could be a promising candidate in the development of effective vaccine for prevention of the infections of newly emergent strains of SARS-CoV-2 virus. EGCG might be useful also as a clinical medicine for treatment of COVID-19 patients if its bioavailability in human plasma is enhanced.

Some natural compounds and their analogues having potent anti- SARS-CoV-2 and anti-proteases activities as lead molecules in drug discovery for COVID-19.

Currently an emerging human pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused coronavirus disease 2019 (COVID-19) that has posed a serious threat to public health worldwide. As it is a novel severe pneumonia-type viral disease, no effective therapeutic agents are available to treat this infection to date, emphasizing an urgent need for development of effective anti-SARS-CoV-2 agents. Based on screening in computational biology and biological in vitro assays, a good number of natural compounds and their synthetic analogues have been confirmed to possess target-specific inhibitory effects against the activity of host and viral proteases, namely, cathepsin-L, TMPRSS2, Sec61, Mpro (3CL-protease), RNA-dependent RNA protease (RdRp), helicase cap-binding proteases eEF1A, eIF4A, eIF4E, which play dominant roles in progression of infection and replication of SARS-CoV-2 virus in host cells. This review paper describes the potent antiviral activity and target-specific anti-proteases activity of some natural compounds and their synthetic analogues against SARS-CoV-2 infection. It will inspire the researchers to unleash their own creativity and to design potent and safe drugs to fight the current COVID-19 pandemic.

Evaluation of wound healing activity of ethanol extract of Annona reticulata L. leaf both in vitro and in diabetic mice model.

BACKGROUND AND AIM: The leaves of AnnonareticulataLinn (niú x inguǒ; Bullock's heart), a member of Annonaceae family, have been used extensively in folk medicine; however, its wound healing potential is yet to be explored. Our aim was to investigate the wound healing ability of A. reticulataleaf extract in vitro and in streptozotocin induced diabetic mice model. MATERIAL AND METHODS: We observed the plant extract induced proliferation and migration of primary human dermal fibroblast (HDF), human skin fibroblast cell line (GM00637) and human keratinocyte cell line (HACAT). The expression of transforming growth factor beta (TGF-ß), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), matrix metalloproteinases (MMP-2, MMP-9), collagen-1, collagen-3, focal adhesion kinase (FAK) were evaluated by Western blot and gelatin zymography. Excisional diabetic wound model was used for in vivo wound healing assay. Furthermore, we processed wound tissue for histological and immunohistochemical study. RESULT: A. reticulata L. leaf extract stimulates proliferation and migration of HDF, skin fibroblast and keratinocyte significantly in a dose dependent manner; expression of TGF-ß, CTGF, VEGF, α-SMA, MMP-2, MMP-9, collagen-1, collagen-3, FAK increased. Additionally, an enhanced expression of phospho-SMAD2, phospho-SMAD3 in the treated cells indicated the activation of TGF-ß signal transduction pathway, similarly increased expression of phospho-AkT suggested activation of PI3/AkT pathway. Expression of CTGF and α-SMA was also increased significantly in wound tissue. Mass spectrometric analysis revealed that mainly two compounds to be present in the extract: quercetin and ß-sitosterol. CONCLUSION: Collective data suggest that A.reticulata leaf extract may have a stimulatory effect in diabetic wound healing.

Dietary plant flavonoids in prevention of obesity and diabetes.

Obesity and diabetes are the most prevailing chronic metabolic diseases worldwide from mainly lipid and glucose metabolic dysfunctions and their incidence is increasing at an alarming high rate. Obesity is characterized by excess fat accumulation in WAT and liver and is the central player of insulin resistance in the peripheral tissues from chronic inflammation, lipotoxicity and gut dysbiosis, and plays a key role for development of type 2 diabetes (T2DM) and vascular diseases. Diabetes mellitus, known as diabetes, is chiefly characterized by hyperglycaemia from impaired insulin secretion and insulin resistance. Several identified mutant genes in insulin secretion and resistance and various environmental factors are considered responsible for the onset of this disease. Currently available oral synthetic drugs, biguanides, incretin mimetic, GLP-1R and PPAR agonists and DPP-4 inhibitors for management of obesity and diabetes have several adverse effects in patients on long-term use. Emerging evidence supports the efficacy of dietary plant flavonoids in prevention and attenuation of obesity and diabetes by the protection and proliferation of pancreatic beta-cells and improvement of their insulin secretory function via activation of cAMP/PKA signaling pathway as well as in the improvement of insulin sensitivity in the peripheral metabolic tisssues for glucose uptake and utilization via inhibition of inflammation, lipotoxicity and oxidative stress. These flavonoids improve GLUT-4 expression and translocation to plasma membrane by activation of insulin-sensitive PI3K/Akt signaling and insulin-independent AMPK, SIRT-1 and MOR activation pathways for regulation of glucose homeostasis, and improve fat oxidation and reduce lipid synthesis by regulation of related genes for lipid homeostasis in the body of obese diabetic animals. In this chapter, we have highlighted all these beneficial anti-obesity and antidiabetic potentials of some dietary plant flavonoids along with their molecular actions, bioavailability and pharmacokinetics. In addition, the present understanding and management of obesity and diabetes are also focused.

Pausing sites of RNA polymerase II on actively transcribed genes are enriched in DNA double-stranded breaks.

DNA double-stranded breaks (DSBs) are strongly associated with active transcription, and promoter-proximal pausing of RNA polymerase II (Pol II) is a critical step in transcriptional regulation. Mapping the distribution of DSBs along actively expressed genes and identifying the location of DSBs relative to pausing sites can provide mechanistic insights into transcriptional regulation. Using genome-wide DNA break mapping/sequencing techniques at single-nucleotide resolution in human cells, we found that DSBs are preferentially located around transcription start sites of highly transcribed and paused genes and that Pol II promoter-proximal pausing sites are enriched in DSBs. We observed that DSB frequency at pausing sites increases as the strength of pausing increases, regardless of whether the pausing sites are near or far from annotated transcription start sites. Inhibition of topoisomerase I and II by camptothecin and etoposide treatment, respectively, increased DSBs at the pausing sites as the concentrations of drugs increased, demonstrating the involvement of topoisomerases in DSB generation at the pausing sites. DNA breaks generated by topoisomerases are short-lived because of the religation activity of these enzymes, which these drugs inhibit; therefore, the observation of increased DSBs with increasing drug doses at pausing sites indicated active recruitment of topoisomerases to these sites. Furthermore, the enrichment and locations of DSBs at pausing sites were shared among different cell types, suggesting that Pol II promoter-proximal pausing is a common regulatory mechanism. Our findings support a model in which topoisomerases participate in Pol II promoter-proximal pausing and indicated that DSBs at pausing sites contribute to transcriptional activation.

A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure.

The NAD+-dependent histone deacetylase Sir2 was originally identified in Saccharomyces cerevisiae as a silencing factor for HML and HMR, the heterochromatic cassettes utilized as donor templates during mating-type switching. MATa cells preferentially switch to MATα using HML as the donor, which is driven by an adjacent cis-acting element called the recombination enhancer (RE). In this study we demonstrate that Sir2 and the condensin complex are recruited to the RE exclusively in MATa cells, specifically to the promoter of a small gene within the right half of the RE known as RDT1. We also provide evidence that the RDT1 promoter functions as a locus control region (LCR) that regulates both transcription and long-range chromatin interactions. Sir2 represses RDT1 transcription until it is removed from the promoter in response to a dsDNA break at the MAT locus induced by HO endonuclease during mating-type switching. Condensin is also recruited to the RDT1 promoter and is displaced upon HO induction, but does not significantly repress RDT1 transcription. Instead condensin appears to promote mating-type donor preference by maintaining proper chromosome III architecture, which is defined by the interaction of HML with the right arm of chromosome III, including MATa and HMR. Remarkably, eliminating Sir2 and condensin recruitment to the RDT1 promoter disrupts this structure and reveals an aberrant interaction between MATa and HMR, consistent with the partially defective donor preference for this mutant. Global condensin subunit depletion also impairs mating-type switching efficiency and donor preference, suggesting that modulation of chromosome architecture plays a significant role in controlling mating-type switching, thus providing a novel model for dissecting condensin function in vivo.

Therapeutic potentials of plant iridoids in Alzheimer's and Parkinson's diseases: A review.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders, affecting several millions of aged people globally. Among these disorders, AD is more severe, affecting about 7% of individuals aged 65 and above. AD is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while PD is primarily a movement disorder illness having three major kinesia or movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. AD is characterized by deposition of extracellular beta-amyloid (Aß) proteins and intracellular neurofibrillary tangles (NFT), composed of hyperphosphorylated tau proteins in the neurons located particularly in hippocampus and cerebral cortex regions of brain, resulting the neuronal loss, while PD is characterized by deposition of intraneuronal aggregates of mostly composed of alpha-synuclein gene as Lewy bodies (LB) in the striatal region, known as substantia nigra pars compacta (SNpc) of brain, leading to the death of dopaminergic neurons. These are known as pathological hallmarks of these diseases. However, in some overlapping cases, known as Alzheimer with Parkinson disease or vice versa, alpha-synuclein deposition in AD and tau deposition in PD patients are found. Oxidative stress-induced glial cells activation, neuroinflammation and mitochondrial dysfunction lead to various molecular events in brain neurons causing neuronal cell death in these neurodegenerative disorders. Currently used drugs for treatment of AD and PD only reduce the symptoms of these diseases, but unable to stop the process of neurodegeneration. Therefore, innovation of new synthetic drugs or discovery of natural drugs for the treatment of AD and PD, is a challenging task of basic science and clinical medicine. Plant iridoids such as catalpol and its 10-O-trans-p-coumaroyl derivative, geniposide, harpagoside, and loganin, and seco-iridoids, oleuropein and its aglycone and oleocanthal have been found to exhibit significant neuroprotective effect and the property of slowing down the process of neurogedeneration in AD and PD. These plant metabolites have been shown to ameliorate AD by increasing the expression of insulin degrading enzyme (IDE), neprilysin (NEP), PPAR-γ, and α-secretase, and decreasing the expression of ß-secretase (BACE-1) to reduce the levels of Aß oligomers (AßO) deposition in brain neurons. These plant metabolites reduced the expression of GSK-3ß and its receptor gene, PTEN to reduce hyperphosphorylation of tau proteins and neurofibrillary tangles (NFTs) formation. These metabolites improved the expressions of neuroprotective proteins, Bcl-2 via activations of growth-related protein-1 receptor (GLP-1R), PKC, MEK, MAPK/PI3K, and AMPK, and suppressed the expressions of pro-apoptotic proteins, Bax and caspase-3. Furthermore, these plant metabolites improved the lysosomal autophagy process by increasing the expression levels of Beclin-1, LC3II and cathepsin B genes for clearance of Aß and NFT, and increased the expression of transporter proteins, P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein-1 (LRP-1) for the clearance of Aß load from brain across the blood-brain barrier (BBB) as well as increased the expression of PPAR-γ and ApoE proteins for clearance of Aß in ApoE mediated pathway from brain. Moreover, these plant metabolites reduced the cognitive impairment by increasing the expression of synaptic proteins, BDNF, PSD-95, SNAP-25, SYP and GAP-43 for improvement of learning and memory functions in AD. While among these iridoids, catalpol, 10-O-trans-p-coumaroylcatalpol, geniposide and harpagoside, in PD improved the expressions of GDNF and Bcl-2 proteins and TH-positive neurons by increasing the levels of antioxidant enzymes, SOD and GSH-PX and down-regulating insulin/IGF signalling via activation of MEK protein. Moreover, catalpol and its p-coumaroyl derivative in mutant nematode C. elegans model, up-regulated the expression of DAF-16, a FOXO family transcription factor and SKN-1 genes for improvement of lifespan and resistance against oxidative- and other stresses of mutated worms. Furthermore, geniposide increased the expression of autophagy-related LAMP-2A-protein for clearance of LB from dopaminergic neurons in PD brain via improving lysosomal autophagy process. The present review summarizes the neuroprotective activities and molecular mechanisms of these iridoids and secoiridoids, in prevention and/or treatment of both AD and PD. This review will be helpful to find out the research gap on these plant metabolites in this field to use them as potential drugs against these disorders.

Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders.

The flavonoids, baicalin (5,6-dihydroxy-2-phenyl-4H-1-benzopyran-4-one-7-O-d-ß-glucuronic acid) 1 and its aglycone, baicalein 2 are found in edible medicinal plants, Scutellaria baicalensis Georgi and Oroxylum indicum (L.) Kurz in abundant quantities. The antioxidant and anti-inflammatory effects of these flavonoids have been demonstrated in various disease models, including diabetes, cardiovascular diseases, inflammatory bowel diseases, gout and rheumatoid arthritis, asthma, neurodegenerative-, liver- and kidney diseases, encephalomyelitis, and carcinogenesis. These flavonoids have almost no toxicity to human normal epithelial, peripheral and myeloid cells. Their antioxidant and anti-inflammatory activities are largely due to their abilities to scavenge the reactive oxygen species (ROS) and improvement of antioxidant status by attenuating the activity of NF-κB and suppressing the expression of several inflammatory cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1), nitric oxide synthase, cyclooxygenases, lipoxygenases, cellular adhesion molecules, tumor necrosis factor and interleukins. In this review, we summarize the antioxidant and anti-inflammatory effects of baicalin and baicalein with molecular mechanisms for their chemopreventive and chemotherapeutic applications in the treatment of inflammatory-related diseases.

Cornus mas L. (cornelian cherry), an important European and Asian traditional food and medicine: Ethnomedicine, phytochemistry and pharmacology for its commercial utilization in drug industry.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus mas L. (cornelian cherry) fruits have been used for centuries as traditional cuisine and folk medicine in various countries of Europe and Asia. In folk medicines, the fruits and other parts of the plant have been used for prevention and treatment of a wide range of diseases such as diabetes, diarrhea, gastrointestinal disorders, fevers, rheumatic pain, skin and urinary tract infections, kidney and liver diseases, sunstroke, among others. This review provides a systematic and constructive overview of ethnomedicinal uses, chemical constituents and pharmacological activities of this plant as well as future research need for its commercial utilization as nutraceutical food supplement and medicine. MATERIALS AND METHODS: This review is based on available literature on ethnomedicinal uses, phytochemical, pharmacological, toxicity and clinical studies on Cornus mas L. (cornelian cherry) fruits and other organs that was collected from electronic (SciFinder, PubMed, Science Direct and ACS among others) and library searches of books and journals. RESULTS: Versatile ethnomedicinal uses of the plant in different European and Asian countries have been reported. Phytochemical investigations on different parts of this plant have resulted in the identification of 101 compounds, among which anthocyanins, flavonoids and iridoids are the predominant groups. The crude extracts of fruits and other parts of the plant and their pure isolates exhibit a broad spectrum of pharmacological activities such as anti-microbial, anti-diabetic, anti-atherosclerotic, cyto-, hepato-, neuro- and renalprotective, antiplatelet and antiglaucomic activities. Anthocyanins, flavonoids, iridoids and vitamin C are the major bioactive constituents of the fruits. Fruits are non-toxic and safe food on acute toxicity studies in rat and human models. Clinical trials in diabetic type2 and hyperlipidemic patients showed significant trends of amelioration in sugar level, insulin secretion in diabetic patients and amelioration of lipid profile, apolipoprotein status and vascular inflammation in hyperlipidemic patients. CONCLUSION: Based on our review, Cornus mas L. (cornelian cherry) fruits and leaves can be used mainly in the treatment of diabetes, obesity, atherosclerosis, skin diseases, gastrointestinal and rheumatic problems. Some indications from ethnomedicines have been validated by pharmacological activities of the fruits and its extracts/pure isolates. The reported data reveal that the fruits are a potential source for treatment of diabetes, obesity, hyperlipidemia and gastrointestinal disorders. Unfortunately, the pharmacological studies in these areas are still insufficient to substantiate these preventive effects in confirmatory trials on the mass-scale clinical settings. Future studies on mechanisms of action, bioavailability, pharmacokinetics and adverse effects of the extracts and their bioactive constituents as well as their effective doses and long term toxic effects in humans are needed for commercial applications of these extracts/isolates in modern medicines. The available literature showed that most of the activities of the extracts are due to their constituents, anthocyanins, flavonoids and other phenolics, iridoids and vitamins for their antioxidant and other properties.

The Water Fraction of Calendula officinalis Hydroethanol Extract Stimulates In Vitro and In Vivo Proliferation of Dermal Fibroblasts in Wound Healing.

The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up-regulate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α-SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC-ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin-3-O-glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α-SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd.

The genus Sida L. - A traditional medicine: Its ethnopharmacological, phytochemical and pharmacological data for commercial exploitation in herbal drugs industry.

ETHNOPHARMACOLOGICAL RELEVANCE: Sida L. (Malvaceae) has been used for centuries in traditional medicines in different countries for the prevention and treatment of different diseases such as diarrhea, dysentery, gastrointestinal and urinary infections, malarial and other fevers, childbirth and miscarriage problems, skin ailments, cardiac and neural problems, asthma, bronchitis and other respiratory problems, weight loss aid, rheumatic and other inflammations, tuberculosis, etc. AIMS OF THIS REVIEW: To assess the scientific evidence for therapeutic potential of Sida L. and to identify the gaps of future research needs. METHODS: The available information on the ethnomedicinal uses, phytochemistry, pharmacology and toxicology of Sida species was collected via a library and electronic searches in SciFinder, PubMed, ScienceDirect, Google Scholar for the period, 1933-2015. RESULTS: A variety of ethnomedicinal uses of Sida species have been found in India, China, Afrian and American countries. Phytochemical investigation of this genus has resulted in identification of about 142 chemical constituents, among which alkaloids, flavonoids and ecdysteroids are the predominant groups. The crude extracts and isolates have exhibited a wide spectrum of in vitro and in vivo pharmacological effects involving antimicrobial, analgesic, anti-inflammatory, abortifacient, neuroprotective, cardiovascular and cardioprotective, antimalarial, antitubercular, antidiabetic and antiobesity, antioxidant and nephroprotective activities among others. Ethnopharmacological preparations containing Sida species as an ingredient in India, African and American countries possess good efficacy in health disorders. From the toxicity perspective, only three Sida species have been assessed and found safe for oral use in rats. CONCLUSIONS: Pharmacological results supported some of the uses of Sida species in the traditional medicine. Alkaloids, flavonoids, other phenolics and ecdysteroids were perhaps responsible for the activities of extracts of the plants of this genus. No clinical study was reported. The detailed study on mechanism of action of isolates and extracts and their clinical study are needed for their use in modern medicine. More attention should be paid to Sida acuta, Sida cordifolia, Sida spinosa, Sida rhombifolia and Sida veronicaefolia in the domain of diarrhea, dysentery, gastrointestinal and urinary infections, skin ailments, asthma, bronchitis and other respiratory problems, malaria, childbirth and miscarriage problems, cardiac and neural problems, weight loss aid, and rheumatic and other inflammations, etc. Furthermore, detailed study on quality and safety assurance data on available ethnopharmacological preparations is needed for their commercial exploitation in local and global markets.

PI3K-mediated proliferation of fibroblasts by Calendula officinalis tincture: implication in wound healing.

Calendula officinalis, a member of the Asteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood. Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K-dependent pathway. The increase in phosphorylation of FAK (Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC-ESI MS revealed the presence of flavonol glycosides as the major compounds of CDOT. Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K-dependent pathway, and the identified compounds are likely to be responsible for wound healing activity.