Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors.

Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling that is usually generated at cell surface receptors and thereby transmit it to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). There is strong evidence to suggest that aberrant STAT3 signaling promotes initiation and progression of human cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. Suppression of STAT3 activation results in the induction of apoptosis in tumor cells, and accordingly its pharmacological modulation by tyrosine kinase inhibitors, antisense oligonucleotides, decoy nucleotides, dominant negative proteins, RNA interference and chemopreventive agents have been employed to suppress the proliferation of various human cancer cells in culture and tumorigenicity in vivo. However, the identification and development of novel drugs that can target deregulated STAT3 activation effectively remains an important scientific and clinical challenge. This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade.

A self-assembled superhydrophobic electrospun carbon-silica nanofiber sponge for selective removal and recovery of oils and organic solvents.

An oil spill needs timely cleanup before it spreads and poses serious environmental threat to the polluted area. This always requires the cleanup techniques to be efficient and cost-effective. In this work, a lightweight and compressible sponge made of carbon-silica nanofibers is derived from electrospinning nanotechnology that is low-cost, versatile, and readily scalable. The fabricated sponge has high porosity (>99 %) and displays ultra-hydrophobicity and superoleophilicity, thus making it a suitable material as an oil adsorbent. Owing to its high porosity and low density, the sponge is capable of adsorbing oil up to 140 times its own weight with its sorption rate showing solution viscosity dependence. Furthermore, sponge regeneration and oil recovery are feasible by using either cyclic distillation or mechanical squeezing.

The multifaceted role of curcumin in cancer prevention and treatment.

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers.

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, and is also the fourth most common cancer worldwide with around 700,000 new cases each year. Currently, first line chemotherapeutic drugs used for HCC include fluorouracil, cisplatin, doxorubicin, paclitaxel and mitomycin, but most of these are non-selective cytotoxic molecules with significant side effects. Sorafenib is the only approved targeted therapy by the U.S. Food and Drug Administration for HCC treatment, but patients suffer from various kinds of adverse effects, including hypertension. The signal-transducer-and-activator-of-transcription 3 (STAT3) protein, one of the members of STATs transcription factor family, has been implicated in signal transduction by different cytokines, growth factors and oncogenes. In normal cells, STAT3 activation is tightly controlled to prevent dysregulated gene transcription, whereas constitutively activated STAT3 plays an important role in tumorigenesis through the upregulation of genes involved in anti-apoptosis, proliferation and angiogenesis. Thus, pharmacologically safe and effective agents that can block STAT3 activation have the potential both for the prevention and treatment of HCC. In the present review, we discuss the possible role of STAT3 signaling cascade and its interacting partners in the initiation of HCC and also analyze the role of various STAT3 regulated genes in HCC progression, inflammation, survival, invasion and angiogenesis.

The rotational advancement of medial plantar flap for coverage of foot defect: a case report.

This case describes the use of the medial plantar artery flap used to cover a lateral foot wound in a 19-year-old male with a history of spina bifida. The original operative plan was for coverage with a medial plantar flap based distally on retrograde flow through the lateral plantar artery; however, this had to be revised intraoperatively as his vascular anatomy was not adequate to support a flap of this type. Thus, advancement with rotation modification of the conventional medial plantar flap was performed with good results. At 2-month follow-up, the patient's flap had fully healed, he returned to full weight-bearing status, and he had gross sensation in the sole of his foot. This case illustrates the use of the well-described medial plantar flap by rotating and advancing the flap for reconstruction of defects of the foot.

Hydrogen sulfide regulates Na+/H+ exchanger activity via stimulation of phosphoinositide 3-kinase/Akt and protein kinase G pathways.

Intracellular pH (pH(i)) is an important endogenous modulator of cardiac function. Inhibition of Na(+)/H(+) exchanger-1 (NHE-1) protects the heart by preventing Ca(2+) overload during ischemia/reperfusion. Hydrogen sulfide (H(2)S) has been reported to produce cardioprotection. The present study was designed to investigate the pH regulatory effect of H(2)S in rat cardiac myocytes and evaluate its contribution to cardioprotection. It was found that sodium hydrosulfide (NaHS), at a concentration range of 10 to 1000 µM, produced sustained decreases in pH(i) in the rat myocytes in a concentration-dependent manner. NaHS also abolished the intracellular alkalinization caused by trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methane-sulfonate hydrate (U50,488H), which activates NHEs. Moreover, when measured with an NHCl(4) prepulse method, NaHS was found to significantly suppress NHE-1 activity. Both NaHS and cariporide or [5-(2-methyl-5-fluorophenyl)furan-2-ylcarbonyl]guanidine (KR-32568), two NHE inhibitors, protected the myocytes against ischemia/reperfusion injury. However, coadministration of NaHS with KR-32568 did not produce any synergistic effect. Functional study showed that perfusion with NaHS significantly improved postischemic contractile function in isolated rat hearts subjected to ischemia/reperfusion. Blockade of phosphoinositide 3-kinase (PI3K) with 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), Akt with Akt VIII, or protein kinase G (PKG) with (9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]]enzodiazocine-10-carboxylic acid, methyl ester (KT5823) significantly attenuated NaHS-suppressed NHE-1 activity and/or NaHS-induced cardioprotection. Although KT5823 failed to affect NaHS-induced Akt phosphorylation, Akt inhibitor did attenuate NaHS-stimulated PKG activity. In conclusion, this work demonstrated for the first time that H(2)S produced cardioprotection via the suppression of NHE-1 activity involving a PI3K/Akt/PKG-dependent mechanism.

Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC ß-lactamase-producing Enterobacteriaceae.

BACKGROUND: Temocillin, a ß-lactam stable against most ß-lactamases [including extended-spectrum ß-lactamases (ESBLs) and derepressed AmpC cephalosporinases (dAmpC)], has been suggested as an alternative to carbapenems when Pseudomonas can be excluded. Aims To assess temocillin clinical and microbiological cure rates (CCR and MCR) in infection caused by ESBL/dAmpC-producing Enterobacteriaceae and the effects of different dosage regimens. METHODS: Data were collected retrospectively from patients treated for at least 3 days with temocillin for urinary tract infection (n = 42), bloodstream infection (n = 42) or hospital-acquired pneumonia (n = 8) in six centres in the UK. RESULTS: Data on 92 infection episodes were collected. Overall CCR and MCR were 86% and 84% respectively; ESBL/dAmpC status had no effect. Significantly higher CCR and MCR occurred in patients treated with temocillin at optimal dosage [2 g twice daily or renally adjusted equivalent (ORAE)] compared with those treated with a suboptimal dosage (<2 g twice daily ORAE) (CCR 91% and MCR 92% versus CCR 73% and MCR 63%). This difference was more pronounced in the ESBL/dAmpC-positive subset (CCR 97% and MCR 97% versus CCR 67% and MCR 50%). CONCLUSIONS: Clinical and microbiological efficacies of temocillin are unaffected by ESBL/dAmpC production, confirming its potential application as a carbapenem-sparing agent. Both CCR and MCR are optimized by a regimen of 2 g twice daily ORAE in ESBL/dAmpC-positive infection.

Polysaccharide-protein complex from Lycium barbarum L. is a novel stimulus of dendritic cell immunogenicity.

Dendritic cell (DC) immunogenicity correlates with its maturation, which can be induced by toxic microbial products such as LPS. In this study, we report that a nontoxic polysaccharide-protein complex isolated from a Chinese medicinal herb, Lycium barbarum (LBP), induces phenotypic and functional maturation of DCs with strong immunogenicity. LBP up-regulated DC expression of CD40, CD80, CD86, and MHC class II molecules; down-regulated DC uptake of Ag; enhanced DC allostimulatory activity; and induced IL-12p40 and p70 production. All of its five fractions were active. LBP developed enhanced Th1 response, and LBP-treated DCs enhanced Th1 and Th2 responses in vitro and in vivo. Our study provides evidence and rationale on using LBP in various clinical conditions to enhance host immunity and suggests LBP as a potent adjuvant for the design of DC-based vaccines.

Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function.

BACKGROUND AND PURPOSE: Oxidative stress is known to be involved in ischemic stroke. Intense interest is drawn to the therapeutic potential of Chinese herbs on ischemic stroke because many of them contain antioxidant properties. Leonurine, 1 of the active compounds from purified Herba Leonuri, was studied to evaluate its possible therapeutic effects on ischemic stroke. Method-Middle cerebral artery occlusion was selected as our model of study. The animals were pretreated with Leonurine orally for 7 days and the surgery was done. One day after surgery, 2,3,5-triphenyltetrazolium chloride staining and neurological deficit score were carried out to evaluate the functional outcome of animals, whereas levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde were analyzed for oxidative stress analysis. For mitochondrial studies, 3 hours after surgery, mitochondria were isolated for analysis of reactive oxygen species production, adenosine triphosphate biosynthesis, oxygen consumption, and respiratory control ratio value. Result-In in vivo experiments, Leonurine pretreatment reduced infarct volume, improved neurological deficit in stroke groups, increased activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase, and decreased levels from the lipid peroxidation marker malondialdehyde. In terms of mitochondrial modulation, Leonurine inhibited mitochondrial reactive oxygen species production and adenosine triphosphate biosynthesis. Animal studies also demonstrated that the mitochondrial function and redox state were restored by Leonurine treatment. CONCLUSIONS: Leonurine has neuroprotective effects and carries a therapeutic potential of stroke prevention.

Baicalin reduces mitochondrial damage in streptozotocin-induced diabetic Wistar rats.

BACKGROUND: Hyperglycemia-induced superoxide production in the mitochondria is known to be the primary cause of diabetic micro- and macro-vascular complications and mitochondrial membranal damage. This study in streptozotocin-induced diabetic Wistar rats investigated the anti-hyperglycemic and mitochondrial membrane protection effects of baicalin, a flavonoid known for its radical scavenging activity. METHODS: The following oral treatments were given to diabetic rats for 30 days: (1) metformin 500 mg/kg, (2) baicalin 120 mg/kg, and (3) metformin 500 mg/kg & baicalin 120 mg/kg, with vehicle-treated diabetic and non-diabetic groups serving as controls. RESULTS: Transmission electron microscopy imaging of pancreatic beta-cells revealed loss of integrity of the inner membrane of the mitochondria in the diabetic rats, which was not observed in the baicalin-treated group. In addition, baicalin and the combined treatment of metformin and baicalin had significantly reduced (p < 0.05) the number of mitochondria with a damaged membrane compared to the diabetic control as well as the metformin-treated group in the hepatic tissues. Baicalin had also increased the plasma leptin content (p < 0.05) versus the diabetic control, which in turn had effected the total expression of hepatic mitochondria per cell indicating its effects in SIRT1 activity. The increase in mitochondrial number was further complemented with similar trends in the hepatic citrate synthase activity. CONCLUSIONS: Baicalin had reduced the hyperglycemia-induced mitochondrial membrane damage, as well as enhanced the effects of metformin, as was observed in the results from the metformin and baicalin treated groups.

Activation of macrophages by polysaccharide-protein complex from Lycium barbarum L.

Macrophages play crucial roles in innate immunity. This paper reports that a polysaccharide-protein complex isolated from Lycium barbarum (LBP) is able to activate macrophages. LBP was isolated from Lycium barbarum fruit and separated to five homogenous fractions, designated LBPF1, LBPF2, LBPF3, LBPF4 and LBPF5. It was found that LBP (50 mg/kg, i.p.) markedly upregulated the expressions of CD40, CD80, CD86 and MHC class II molecules on peritoneal macrophages. In vitro studies showed that LBP and LBPF1-5 activated transcription factors NF-kappaB and AP-1 by RAW264.7 macrophage cells, induced TNF-alpha, IL-1beta, IL-12p40 mRNA expression, and enhanced TNF-alpha production in a dose-dependent manner. Furthermore, LBP (50 mg/kg, i.p.) significantly enhanced macrophage endocytic and phagocytic capacities in vivo. These results indicate that LBP enhances innate immunity by activating macrophages. The mechanism may be through activation of transcription factors NF-kappaB and AP-1 to induce TNF-alpha production and upregulation of MHC class II costimulatory molecules.

Activation of T lymphocytes by polysaccharide-protein complex from Lycium barbarum L.

T lymphocytes play central roles in adaptive immunity. Lycium barbarum L. (L. barbarum), also known as wolfberry, is a Chinese herbal medicine with various biological activities, such as enhancing immunity, protecting liver damage, and reducing the side effects of chemotherapy and radiotherapy. Here, we report that polysaccharide-protein complex from L. barbarum (LBP) is able to activate T cells. LBP was isolated from L. barbarum and separated to five homogenous fractions, designated LBPF1, LBPF2, LBPF3, LBPF4, and LBPF5. We found that LBP, LBPF4, and LBPF5 significantly stimulated mouse splenocyte proliferation. The proliferation proved to be of T cells, but not B cells. Cell cycle profile analysis indicated that LBP, LBPF4, and LBPF5 markedly reduced sub-G1 cells. LBP, LBPF4, and LBPF5 could activate transcription factors NFAT and AP-1, prompt CD25 expression, and induce IL-2 and IFN-gamma gene transcription and protein secretion. LBP (i.p. or p.o.) significantly induced T cell proliferation. Our results suggest that activation of T lymphocytes by LBP may contribute to one of its immuno-enhancement functions.

Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats.

Oxidative stress is the root cause of diabetic macro- and microvascular complications. Biochemical and epidemiological studies indicate that current treatments for diabetes do not reduce risks of developing complications, suggesting their inability to alleviate the levels of oxidative stress. This study in streptozotocin (STZ)-induced diabetic rats was carried out to investigate the effect of combining the antidiabetic drug, metformin, with an ethanolic extract of Scutellaria baicalensis, a plant whose root is known for its radical scavenging activity. Three groups of STZ-induced diabetic rats were given the following treatments for 30 days: (1) metformin 500 mg/kg, (2) S. baicalensis 400 mg/kg, (3) metformin 500 mg/kg + S. baicalensis extract 400 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The rats treated with S. baicalensis and metformin + S. baicalensis had elevated hepatic activities of the antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared to the vehicle- and metformin-treated diabetic groups (p < 0.05). Plasma and hepatic lipid peroxide concentrations in the herb-treated and herb + metformin-treated groups were also significantly reduced (p < 0.05). In addition, the combined treatment caused significant elevations of plasma and pancreatic insulin levels and reductions of plasma and hepatic triglycerides (TG) and cholesterol levels. The study thus showed that S. baicalensis enhanced the antidiabetic effect of metformin in STZ-induced diabetic rats by improving the antioxidant status. It also increased pancreatic insulin content as well as improved the lipid profile in these rats.

Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats.

This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.

Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides.

BACKGROUND: Plants containing compounds such as the isoflavonoids, with female hormone-like effects that bind to human estrogen receptors, are known. But none has been previously shown to have corresponding male hormone-like effects that interact with the human androgen receptor. Here, we report that the tree bark (cortex) of the Gutta-Percha tree Eucommia ulmoides possesses bimodal phytoandrogenic and hormone potentiating effects by lipidic components. METHODS: The extracts of E. ulmoides were tested using in-vitro reporter gene bioassays and in-vivo animal studies. Key compounds responsible for the steroidogenic effects were isolated and identified using solid phase extraction (SPE), high performance liquid chromatography (HPLC), thin layer chromatography (TLC), gas chromatography-mass spectroscopy (GC-MS), electron spray ionisation-mass spectroscopy (ESI-MS) and nuclear magnetic resonance (NMR). RESULTS: The following bioactivities of E. ulmoides were found: (1) a phenomenal tripartite synergism exists between the sex steroid receptors (androgen and estrogen receptors), their cognate steroidal ligands and lipidic augmenters isolated from E. ulmoides, (2) phytoandrogenic activity of E. ulmoides was mediated by plant triterpenoids binding cognately to the androgen receptor (AR) ligand binding domain. CONCLUSION: In addition to well-known phytoestrogens, the existence of phytoandrogens is reported in this study. Furthermore, a form of tripartite synergism between sex steroid receptors, sex hormones and plant-derived lipids is described for the first time. This could have contrasting clinical applications for hypogonadal- and hyperlipidaemic-related disorders.

Rumex dentatus Inhibits Cell Proliferation, Arrests Cell Cycle, and Induces Apoptosis in MDA-MB-231 Cells through Suppression of the NF-κB Pathway.

Background:Rumex dentatus, commonly known as tooth docked, is widely used in traditional system of medicines. Although it is well reported for its biological activities and medicinal value, only few studies have been carried out to assess its anticancer potential. Purpose: This study seeks to evaluate the anticancer activity of leaf extracts of R. dentatus against breast cancer MDA-MB-231 cell line, a triple negative human breast cancer cell line with invasive properties and to identify the molecular targets underlying its mechanism of action. Methods: Cytotoxicity of plant extracts was determined against breast cancer cells, using the MTT assay. Flow cytometry was performed to analyze the changes in cell cycle and apoptotic effect, if any. Cells were also studied for their wound healing and invasive potential as well as for Western blotting of apoptotic genes and nuclear factor-kappaB (NF-κB) pathway. Results: The results revealed that R. dentatus methanol (RM) and chloroform (RC) extracts of R. dentatus had the highest inhibition of cell proliferation in a concentration- and time-dependent manner. This inhibitory effect was found to be linked to arrest of cell cycle at the G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. Moreover, it was shown that both RM and RC inhibited the proliferation of the malignant cells and induced apoptosis by repressing the activation of NF-κB and its subsequent transcripts, Bcl-xl, Bcl-2, Cyclin D1, survivin, and XIAP. Apoptosis was also confirmed in the cells as suggested by caspase-3 detection. RM and RC also abrogated IκBa phosphorylation in the malignant cells as well as reduced the invasive and migratory capabilities of these cells. Conclusion: Our findings suggest that the methanol and chloroform extracts of R. dentatus may have anti-cancer compounds that are potentially useful in the treatment of human breast cancer.

Oxidative stress: apoptosis in neuronal injury.

Apoptosis has been well documented to play a significant role in cell loss during neurodegenerative disorders, such as stroke, Parkinson disease, and Alzheimer's disease. In addition, reactive oxygen species (ROS) has been implicated in the cellular damage during these neurodegenerative disorders. These ROS can react with cellular macromolecular through oxidation and cause the cells undergo necrosis or apoptosis. The control of the redox environment of the cell provides addition regulation in the signal transduction pathways which are redox sensitive. Recently, many researches focus on the relationship between apoptosis and oxidative stress. However, till now, there is no clear and defined mechanisms that how oxidative stress could contribute to the apoptosis. This review hopes to make clear that generation of ROS during brain injury, particularly in ischemic stroke and Alzheimer's Disease, and the fact that oxidative state plays a key role in the regulation and control of the cell survival and cell death through its interaction with cellular macromolecules and signal transduction pathway, and ultimately helps in developing an unique therapy for the treatment of these neurodegenerative disorders.

Flexible Hierarchical TiO2/Fe2O3 Composite Membrane with High Separation Efficiency for Surfactant-Stabilized Oil-Water Emulsions.

Globally, efficient oil-water separation for surfactant-stabilized oil-water emulsions has been in urgent demand. The current options available for separation are neither sustainable nor resistant to fouling. Herein, we introduce a hierarchically nanostructured TiO2/Fe2O3 composite membrane, which is capable of separating surfactant-stabilized oil-water emulsions with high separation efficiency. The high oil rejection rate is contributed by the acquisition of an interconnected delicate network and underwater superoleophobic interface. Meanwhile, its self-cleaning function promote the facile recovery of the contaminated membrane. Furthermore, the mechanical flexible characteristic of the TiO2/Fe2O3 composite membrane widens its applicability in industrial employment. Thanks to these properties, this novel membrane can be considered as a practical option for treating surfactant-stabilized oil-water emulsions.

Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection.

OBJECTIVE: To evaluate the in vitro activities of the ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). METHODS: The antiviral activities of various concentrations of the EA fraction of H. cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Cinanserin hydrochloride was also tested against MHV. The EA fraction of H. cordata was tested for acute oral toxicity in C57BL/6 mice. RESULTS: The EA fraction of H. cordata inhibited viral infectivity up to 6 d. Cinanserin hydrochloride was able to inhibit MHV for only 2 d. The 50% inhibitory concentrations (IC50) of the EA fraction of H. cordata added before the viral adsorption stage were 0.98 µg/mL for MHV and 7.50 µg/mL for DENV-2 with absence of cytotoxicity. The mice fed with the EA fraction up to 2000 mg/kg did not induce any signs of acute toxicity, with normal histological features of major organs. Certain flavonoids exhibited comparatively weaker antiviral activity, notably quercetin which could inhibit both MHV and DENV-2. This was followed by quercitrin which could inhibit DENV-2 but not MHV, whereas rutin did not exert any inhibitory effect on either virus. When quercetin was combined with quercitrin, enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed. However, the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction. CONCLUSIONS: The compounds in H. cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo. H. cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.