OBJECTIVE:To explore the best therapy for infertility caused by polycystic ovary syndrome (PCOS).

METHODS:One hundred and twenty patients were randomized into three groups, a clomi-phene group (group A), an acupuncture-moxibustion + Chinese medicine group (group B) and a clomiphene + acupuncture-moxibustion+ Chinese medicine group (group C), 40 cases in each one. In the group A, since the 5th day of menstruation, clomiphene was prescribed for oral administration. In the group B, on the 5th day of menstruation, warm needling therapy was applied at Zhongji (CV 3), Guanyuan (CV 4), Guilai (ST 29), etc. Additionally, the Chinese herbal medication for tonifying the kidney and activating blood circulation was provided. In the group C, the therapy as the group B was combined on the basis of the treatment as the group A. The treatment lasted continuously for 3 menstrual cycles. The endometrial thickness, endometrial type and cervical mucus score on human chorionic gon adotropin (HCG) day, and ovulatory cycle rate, clinical pregnancy rate and abortion rate after treatment were observed in the patients of the three groups.

RESULTS:1) HCG day cervical mucus score, endometrial thickness and endometrial morphology (A type rate): the results in the group C were better than those in the group A (all P<0.01); the results in the group B were better than those in the group A (all P<0.05). The difference in the endometrial thickness was not significant in comparison between the group C and the group B (P>0.05). The cervical mucus score and endometrial morphology (A type rate) in the group C were better than those in the group B (both P<0.05). 2) The ovulatory cycle rates in the group A and group (C were higher than that in the group B (both P<0.05), the pregnancy rate in the group C was higher than that in the other groups (both P<0.05), and the early abortion rate in the group C was lower than that in the group A and group B (both P<0.01). 3) Follicle diameter from 18 mm to 20 mm and endometrial thickness: the differences were not significant between the normal pregnancy patients and the early abortion patients (both P>0.05). The endometrial morphology A type rate in the normal pregnancy patients was higher than that in the early abortion patients (P<0.05).

CONCLUSION:The combined therapy of acupuncture, herbal medicine and clomiphene improves the pregnancy rate and reduces early abortion rate by effectively improving HCG day cervical mucus, endometrial thickness and morphology. The efficacy is apparently superior to the simple medication with clomiphene and the combined application of acupuncture and herbal medicine.

Corneal neovascularization is a significant, sight-threatening complication of many ocular surface disorders. Various growth factors and proteinases are involved in corneal neovascularization. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of VEGF and MMPs is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has been demonstrated for reducing VEGF and MMPs secretion by various cells. Moreover, NM can inhibit endothelial cell migration and capillary tube formation. We herein note that topical application of NM is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations in animal models are needed to place NM alongside corneal neovascularization therapeutics.

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine] is a major alkaloid in tobacco products and has proven to be a potential genotoxic compound. Many natural dietary products can suppress the DNA adduction, and hence act as inhibitors of cancer. In this study, we investigated the inhibitory effects of curcumin, garlic squeeze, grapeseed extract, tea polyphenols, vitamin C, and vitamin E on nicotine-DNA adduction in vivo using an ultrasensitive method of accelerator mass spectrometry (AMS). The results demonstrated that all the dietary constituents induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the control. The reduction rate reached about 50% for all agents, except garlic squeeze (40%), even at its highest dose level. Amongst the six agents, grapeseed extract exhibited the strongest inhibition to the DNA adduct formation. Therefore, we may arrive at a point that these dietary constituents are beneficial to prevent the harmful adduct formation, and thus to block the potential carcinogenesis induced by nicotine.

Sulfuric-flavored compounds were extracted from shiitake (Lentinus edodes) and their inhibitory activity against platelet aggregation was investigated. Platelet aggregation induced by arachidonic acid and U-46619, the analog of thromboxane A(2), was inhibited by the essential oil from shiitake that contained lenthionine as a major sulfuric compound. This result indicates that the inhibitory site of the shiitake flavor compounds would be different from that of garlic-flavor compounds because the latter inhibits the passage between arachidonic acid and thromboxane A(2). The effect of the synthesized lenthionine was almost equivalent to that of the essential oil, which indicates that the inhibitory activity of the essential oil from shiitake would be mainly attributed to lenthionine.

Degradation of extracellular matrix (ECM) is a hallmark of tumor invasion, metastasis and angiogenesis. Based on the Rath multitargeted approach to cancer using natural substances to control ECM stability and enhancing its strength, we developed a novel formulation (NM) of lysine, proline, ascorbic acid and green tea extract that has shown significant anti-cancer activity against a number of cancer cell lines. The aim of the present study was to determine whether NM exhibits anti-angiogenic and anti-metastatic effects using in vitro and in vivo experimental models. Angiogenesis was measured using a chorioallantoic membrane (CAM) assay in chick embryos and bFGF-induced vessel growth in C57BL/6J female mice. To determine the in vivo effect of NM on the tumor xenograft growth, male nude mice were inoculated with 3 x 10(6) MNNG-HOS cells. Control mice were fed a mouse chow diet, while the test group was fed a mouse chow diet supplemented with 0.5% NM for 4 weeks. In vitro studies on cell proliferation (MTT assay), MMP expression (zymography) and Matrigel invasion were conducted on human osteosarcoma U2OS, maintained in McCoy medium, supplemented with 10% FBS, penicillin and streptomycin in 24-well tissue culture plates and tested with NM at 0, 10, 50, 100, 500, and 1000 microg/ml in triplicate at each dose. NM at 250 microg/ml caused a significant (p<0.05) reduction in bFGF-induced angiogenesis in CAM. NM inhibited tumor growth of osteosarcoma MNNG-HOS cell xenografts in nude mice by 53%; furthermore, tumors in NM-treated mice were less vascular and expressed lower levels of VEGF and MMP-9 immunohistochemically than tumors in the control group. In addition, NM exhibited a dose-dependent inhibition of osteosarcoma U2OS cell proliferation (up to 60% at 1000 microg/ml), MMP-2 and -9 expression (with virtual total inhibition at 500 microg/ml NM), and invasion through Matrigel (with total inhibition at 100 microg/ml NM). Moreover, NM decreased U2OS cell expression of VEGF, angiopoietin-2, bFGF, PDGF and TGFbeta-1. These results together with our earlier findings suggest that NM is a relatively non-toxic formulation, which inhibits growth, invasion, metastasis, and angiogenesis of tumor cells.

From the fruiting bodies of the edible mushroom Lentinus edodes, a novel protein designated lentin with potent antifungal activity was isolated. Lentin was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and Mono S. The N-terminal sequence of lentin manifested similarity to endoglucanase. Lentin, which had a molecular mass of 27.5 kDa, inhibited mycelial growth in a variety of fungal species including Physalospora piricola, Botrytis cinerea and Mycosphaerella arachidicola. Lentin also exerted an inhibitory activity on HIV-1 reverse transcriptase and proliferation of leukemia cells.

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Neurodegenerative disease is defined as a deterioration of the nervous system in the intellectual and cognitive capabilities. Statistics show that more than 80-90 million individuals age 65 and above in 2050 may be affected by neurodegenerative conditions like Alzheimer's and Parkinson's disease. Studies have shown that out of 2000 different types of edible and/or medicinal mushrooms, only a few countable mushrooms have been selected until now for neurohealth activity. Hericium erinaceus is one of the well-established medicinal mushrooms for neuronal health. It has been documented for its regenerative capability in peripheral nerve. Another mushroom used as traditional medicine is Lignosus rhinocerotis, which has been used for various illnesses. It has been documented for its neurite outgrowth potential in PC12 cells. Based on the regenerative capabilities of both the mushrooms, priority was given to select them for our study. The aim of this study was to investigate the potential of H. erinaceus and L. rhinocerotis to stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina from chick embryo when compared to brain derived neurotrophic factor (BDNF). Neurite outgrowth activity was confirmed by the immu-nofluorescence method in all tissue samples. Treatment with different concentrations of extracts resulted in neuronal differentiation and neuronal elongation. H. erinaceus extract at 50µg/mL triggered neurite outgrowth at 20.47%, 22.47%, and 21.70% in brain, spinal cord, and retinal cells. L. rhinocerotis sclerotium extract at 50 µg/mL induced maximum neurite outgrowth of 20.77% and 24.73% in brain and spinal cord, whereas 20.77% of neurite outgrowth was observed in retinal cells at 25 µg/mL, respectively.

BACKGROUND:Cimicifuga rhizome, Meliae cortex, Coptidis rhizome and Phellodendron cortex have been previously shown to exhibit anti-coronavirus activity. Here, an additional 19 traditional medicinal herbal extracts were evaluated for antiviral activities in vitro.

METHODS:A plaque assay was used to evaluate the effects of 19 extracts, and the concentration of extract required to inhibit 50% of the replication (EC(50)) of mouse hepatitis virus (MHV) A59 strain (MHV-A59) was determined. The 50% cytotoxic concentration (CC(50)) of each extract was also determined. Northern and western blot analyses were conducted to evaluate antiviral activity on viral entry, viral RNA and protein expression, and release in MHV-infected DBT cells.

RESULTS:Sophorae radix, Acanthopanacis cortex and Torilis fructus reduced intracellular viral RNA levels with comparable reductions in viral proteins and MHV-A59 production. The extracts also reduced the replication of the John Howard Mueller strain of MHV, porcine epidemic diarrhoea virus and vesicular stomatitis virus in vitro. Sanguisorbae radix reduced coronavirus production, partly as a result of decreased protein synthesis, but without a significant reduction in intracellular viral RNA levels. The EC(50) values of the four extracts ranged from 0.8 to 3.7 microg/ml, whereas the CC(50) values ranged from 156.5 to 556.8 microg/ml. Acanthopanacis cortex and Torilis fructus might exert their antiviral activities in MHV-A59-infected cells by inducing cyclooxygenase-2 expression via the activation of extracellular signal-related kinase (ERK) and p38 or ERK alone, respectively.

CONCLUSIONS:Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus might be considered as promising novel anti-coronavirus drug candidates.

BACKGROUND:Cimicifuga rhizome, Meliae cortex, Coptidis rhizome and Phellodendron cortex have been previously shown to exhibit anti-coronavirus activity. Here, an additional 19 traditional medicinal herbal extracts were evaluated for antiviral activities in vitro.

METHODS:A plaque assay was used to evaluate the effects of 19 extracts, and the concentration of extract required to inhibit 50% of the replication (EC(50)) of mouse hepatitis virus (MHV) A59 strain (MHV-A59) was determined. The 50% cytotoxic concentration (CC(50)) of each extract was also determined. Northern and western blot analyses were conducted to evaluate antiviral activity on viral entry, viral RNA and protein expression, and release in MHV-infected DBT cells.

RESULTS:Sophorae radix, Acanthopanacis cortex and Torilis fructus reduced intracellular viral RNA levels with comparable reductions in viral proteins and MHV-A59 production. The extracts also reduced the replication of the John Howard Mueller strain of MHV, porcine epidemic diarrhoea virus and vesicular stomatitis virus in vitro. Sanguisorbae radix reduced coronavirus production, partly as a result of decreased protein synthesis, but without a significant reduction in intracellular viral RNA levels. The EC(50) values of the four extracts ranged from 0.8 to 3.7 microg/ml, whereas the CC(50) values ranged from 156.5 to 556.8 microg/ml. Acanthopanacis cortex and Torilis fructus might exert their antiviral activities in MHV-A59-infected cells by inducing cyclooxygenase-2 expression via the activation of extracellular signal-related kinase (ERK) and p38 or ERK alone, respectively.

CONCLUSIONS:Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus might be considered as promising novel anti-coronavirus drug candidates.

Mushrooms are a source of dietary fiber (DF) with a cholesterol-lowering effect. However, their underlying mechanisms are poorly understood. The effect of DF-enriched fractions from three mushrooms species on cholesterol-related expression was studied in vitro. The Pleurotus ostreatus DF fraction (PDF) was used in mice models to assess its potential palliative or preventive effect against hypercholesterolemia. PDF induced a transcriptional response in Caco-2 cells, suggesting a possible cholesterol-lowering effect. In the palliative setting, PDF reduced hepatic triglyceride likely because Dgat1 was downregulated. However, cholesterol-related biochemical data showed no changes and no relation with the observed transcriptional modulation. In the preventive setting, PDF modulated cholesterol-related genes expression in a manner similar to that of simvastatin and ezetimibe in the liver, although no changes in plasma and liver biochemical data were induced. Therefore, PDF may be useful reducing hepatic triglyceride accumulation. Because it induced a molecular response similar to hypocholesterolemic drugs in liver, further dose-dependent studies should be carried out.

Cholesterol levels are strictly regulated to maintain its homeostasis; therefore, if it is not absorbed with the diet, the cholesterol biosynthetic pathway is enhanced and vice versa. Nowadays, the commonly prescribed therapeutic treatments for hypocholesterolemic patients are targeted toward the reduction of both cholesterol intestinal absorption and/or its endogenous biosynthesis. But, when hypercholesterolemia is still moderate the consumption of food products with cholesterol-lowering capacities is more desirable than using drugs. Marketed foods supplemented with hypocholesterolemic compounds are only inhibiting mechanisms for cholesterol absorption (i.e. phytosterols and cerealβ-glucans). However, certain fungal extracts obtained from edible mushrooms might be able to modulate cholesterol levels by both strategies, pharmaceutical drugs and functional foods. In vitro and in vivo studies indicated that fungal sterols down-regulated genes involved in cholesterol homeostasis(such as Srebf2 and Nr1h4 (FXR)) and other specific mushroom extracts (β-glucans and other water-soluble compounds) also stimulated transcriptional profiles similar to simvastatin or ezetimibe (two hypocholesterolemic drugs). These and other observations suggested that the hypocholesterolemic effect of mushroom extracts could be due to transcriptional and post-transcriptional modulations besides other indirect effects.

AIM:We tested the hypothesis that administrations of methanolic extracts of Musa sapientum sucker (MEMS) with exercises attenuated hyperglycemia in alloxan-diabetic rats.

MATERIALS AND METHODS:A total of 40 adult male rats were divided into equal eight groups. Normoglycemic Group A was Control. Alloxan (180 mg/kg, i.p.) was administered to rats in Groups B - H to induce diabetes. Group B (diabetic control) received physiological saline. Groups C - H received MEMS (5 mg/kg), MEMS (10 mg/kg), Glibenclamide (5 mg/kg), MEMS (5 mg/kg) + exercises, MEMS (10 mg/kg) + exercises and Exercises only, respectively. Changes in body weight, blood glucose levels (BGL) and pancreatic histology were evaluated during or at the end of experiment. Body weights and BGL of rats were expressed as mean± standard deviation and analyzed using the statistical software program SPSS 15. Statistical comparisons were done using the Student's t-test for unpaired samples. Differences between groups were determined as significant at P ≤ 0.05.

RESULTS:Significantly (P<0.05) decreased bodyweight was observed in B and H compared to A and C - G. Treatment with MEMS significantly (P<0.05) decreased elevated BGL in C and D. Hypoglycemic effect of MEMS appeared enhanced with exercises in F and G. Exercises regimen alone (H) resulted in percentage reduction in BGL lower than those of C - G. Histopathological examinations revealed normal pancreas (A), atrophied islet cells (B), hyperplasia with adequate population of islet cells (C - G), and reduced hyperplasia of islet cells (H).

CONCLUSION:MEMS with exercises attenuated hyperglycemia in alloxan-diabetic rats.

BACKGROUND:First line antibiotic treatment of uncomplicated acute otitis media has been questioned.

PATIENTS AND METHODS:In an prospective, open, controlled study, 390 children aged 1-10 years were treated either conventionally (free combinations of decongestant nose drops, mucolytics, analgesics and antibiotics) or alternatively with Otovowen, supplemented by conventional medications when considered necessary.

RESULTS:Patients treated conventionally took more antibiotics (80.5% vs 14.4%) and analgesics (66.8% vs 53.2%). The time to recovery (5.3 vs 5.1 days) and absence from school or pre-school nursery (both 1.7 days) were not significantly different between groups. Pain resolution was slightly better with conventional treatment (-5.8 vs -5.2 score points). The alternative treatment was judged both by doctors, and parents, to be significantly better tolerated.

CONCLUSION:In uncomplicated acute otitis media of childhood, an alternative treatment strategy with the natural medicine Otovowen may substantially reduce the use of antibiotics without disadvantage to the clinical outcome.

BACKGROUND:First line antibiotic treatment of uncomplicated acute otitis media has been questioned.

PATIENTS AND METHODS:In an prospective, open, controlled study, 390 children aged 1-10 years were treated either conventionally (free combinations of decongestant nose drops, mucolytics, analgesics and antibiotics) or alternatively with Otovowen, supplemented by conventional medications when considered necessary.

RESULTS:Patients treated conventionally took more antibiotics (80.5% vs 14.4%) and analgesics (66.8% vs 53.2%). The time to recovery (5.3 vs 5.1 days) and absence from school or pre-school nursery (both 1.7 days) were not significantly different between groups. Pain resolution was slightly better with conventional treatment (-5.8 vs -5.2 score points). The alternative treatment was judged both by doctors, and parents, to be significantly better tolerated.

CONCLUSION:In uncomplicated acute otitis media of childhood, an alternative treatment strategy with the natural medicine Otovowen may substantially reduce the use of antibiotics without disadvantage to the clinical outcome.

We studied whether combinations of botanical extracts enriched in eitherΔ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of Δ(9)-THC- and CBD-enriched botanical extracts. The issue was also studied in malonate-lesioned rats. The administration of Δ(9)-THC- and CBD-enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB(1) receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Δ(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicatedrats by the 1:1 combination of Δ(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies.

Nutrient levels in buckwheats that were maximized in day 8 sprouts (D8SP) included total phenolics, quercetin, and l-ascorbic acid, whereas those of oxalic, malic, tartaric, and citric acids, rutin, and gamma-aminobutyric acid (GABA) were found to reach maximum levels on day 10. Ethanolic extract of D8SP (2.5 mg/mL) revealed potent free-radical scavenging (FRS) and antioxidative (ANO) capabilities. However, its Fe2+-chelating capability was only moderate. To further study the hypolipidemic activity of D8SP, 36 Syrian hamsters were grouped into six groups and fed for 28 days, respectively, with (i) control meal, (ii) high fat plus high cholesterol meal, (iii) high fat plus high cholesterol plus 2.5% of buckwheat seeds, (iv) high fat plus high cholesterol plus 25% of buckwheat seeds, (v) high fat plus high cholesterol plus 2.5% of D8SP, and (vi) high fat plus high cholesterol plus 25% of D8SP. High seed meal prominently enhanced body weight gain, whereas high sprout meal exhibited the highest feed efficiency. Ratios of liver/body weight (L/B) were significantly lowered by all BS meals. Although low seed meal reduced serum total cholesterol (TC) levels (p<0.05), its effect was still inferior to the high seed and sprout meals (p<0.01). In contrast, serum triglyceride (TG) levels were lowered only by the high seed and sprout meals (p<0.05). Alternatively, levels of serum low-density lipoprotein cholesterol (LDL-C) were significantly suppressed by all buckwheat meals (p<0.01). Serum high-density lipoprotein cholesterol (HDL-C) levels were increased, however, insignificantly. Nutraceutically more meaningful is that both LDL-C/HDL-C and TC/HDL-C ratios were significantly lowered (p<0.01). Apparently, hepatic TC levels were significantly reduced, whereas hepatic TG levels were totally unaffected. Conclusively, sprouting triggers a variety of nutritional changes in buckwheats. Day 8 sprouts, consisting of high polyphenolic and moderate quercetin contents, are nutraceutically maximized when hypocholesterolemic, hypotriglyceridemic, and antioxidative activities are concerned.

Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm(-2)) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.

Mushrooms are valuable sources of biologically active compounds possessing anticancer, antiplatelet, and anti-inflammatory properties. Phellinus baumii is a mushroom used in folk medicine for a variety of human diseases. However, its potential anti-inflammatory effect has remained unclear. Therefore, we studied the effect of P. baumii ethyl acetate extract (PBEAE) on inflammatory mediator and proinflammatory cytokine protein and/or mRNA expression levels using the nitric oxide (NO) assay, enzyme immunoassay (EIA), western blot, and reverse transcription polymerase chain reaction (RT-PCR) in lipopolysaccharide (LPS)-stimulated macrophage like RAW264.7 cells. PBEAE markedly inhibited NO generation and prostaglandin E(2) (PGE(2)) synthesis in a concentration-dependent pattern without any cytotoxic effect at the concentration range used. PBEAE also suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. In addition, LPS-induced iNOS and COX-2 mRNA expression levels were dose-dependently inhibited by PBEAE pretreatment. Furthermore, PBEAE attenuated the mRNA expression levels of proinflammatory cytokines, specifically interleukin (IL)-1β, IL-6, and granulocyte macrophage colony-stimulating factor (GM-CSF), in a concentration-dependent fashion. Our study suggests that P. baumii might exhibit anti-inflammatory properties by downregulating proinflammatory mediators. Thus, further study on compounds isolated from PBEAE is warranted to investigate the associated molecular mechanisms and identify the potential therapeutic targets.