GROWTH INHIBITORY EFFECT OF HOUTTUYNIA CORDATA EXTRACT ON STREPTOCOCCUS MUTANS.

Houttuynia cordata is an herbal plant distributed throughout Asia. H. cordata has many bioactive properties, including antibacterial properties. The antibacterial effects of H. cordata on S. mutans remain unknown. Therefore, we treated S. mutans with 1, 3, 5, 10, 20, 30, or 40 mg/mL H. cordata extract at 37°C for 24 h. The antibacterial effect of H. cordata against S. mutans was confirmed using colony forming unit assay and disk diffusion assays. The results of the cell concentration assay demonstrated that H. cordata inhibited the growth of S. mutans in a dose-dependent manner. Prominent growth inhibition was observed after treatment with 10 mg/mL H. cordata extract, and these findings were statistically significant. In addition, no colonies of S. mutans were detected after treatment with 40 mg/mL H. cordata. Disk diffusion assays revealed that 20 mg/mL of H. cordata created a zone of growth inhibition of 11 mm. Therefore, our findings suggest the possibility of using H. cordata in the treatment and prevention of dental caries.

Evaluating the Efficacy of Hymexazol in Controlling Globisporangium spinosum, the Newly Identified Pathogen Causing Root Rot in Houttuynia cordata.

Houttuynia cordata is a prevalent vegetable in several Asian countries and is commonly used as a traditional Chinese medicinal herb for treating various diseases in China. Unfortunately, its yield and quality are adversely affected by root rot. However, the pathogen responsible for the losses remains unidentified, and effective fungicides for its management have not been thoroughly explored. In this work, we demonstrate the first report of Globisporangium spinosum as the causative agent causing root rot of H. cordata. Moreover, we evaluated the efficacy of hymexazol to manage the disease, which displayed remarkable inhibitory effects against mycelial growth of G. spinosum in vitro, with EC50 values as low as 1.336 µg/ml. Furthermore, hymexazol completely inhibited sporangia in G. spinosum at a concentration of 0.3125 µg/ml. Specifically, we observed that hymexazol was highly efficacious in reducing the incidence of H. cordata root rot caused by G. spinosum in a greenhouse setting. These findings offer a potential management tool for utilization of hymexazol in controlling H. cordata root rot in field production.

Endophytic Pseudomonas fluorescens promotes changes in the phenotype and secondary metabolite profile of Houttuynia cordata Thunb.

The interactions between microbes and plants are governed by complex chemical signals, which can forcefully affect plant growth and development. Here, to understand how microbes influence Houttuynia cordata Thunb. plant growth and its secondary metabolite through chemical signals, we established the interaction between single bacteria and a plant. We inoculated H. cordata seedlings with bacteria isolated from their roots. The results showed that the total fresh weight, the total dry weight, and the number of lateral roots per seedling in the P. fluorescens-inoculated seedlings were 174%, 172% and 227% higher than in the control seedlings. Pseudomonas fluorescens had a significant promotional effect of the volatile contents compared to control, with ß-myrcene increasing by 192%, 2-undecanone by 203%, decanol by 304%, ß-caryophyllene by 197%, α-pinene by 281%, bornyl acetate by 157%, γ-terpinene by 239% and 3-tetradecane by 328% in P. fluorescens-inoculated H. cordata seedlings. the contents of chlorogenic acid, rutin, quercitin, and afzelin were 284%, 154%, 137%, and 213% higher than in control seedlings, respectively. Our study provided basic data to assess the linkages between endophytic bacteria, plant phenotype and metabolites of H. cordata to provide an insight into P. fluorescens use as biological fertilizer, promoting the synthesis of medicinal plant compounds.

Houttuynia Cordata Thunb.: A comprehensive review of traditional applications, phytochemistry, pharmacology and safety.

BACKGROUND: Houttuynia Cordata Thunb. (H. cordata; Saururaceae) is a medicine food homology plant that is grown in many Asian countries. Its main phytochemical constituents are volatile oils, flavonoids, polysaccharides and alkaloids. It has considerable clinical applications and health benefits. PURPOSE: This paper reviews the existing literatures and patents, summarizes the phytochemistry, pharmacological activity, safety and economic botanical applications of H. cordata, and provides a reference for systematic study of the pharmacological effects of H. cordata, improvement of quality standards and further development of its medicinal resources. METHODS: A comprehensive search of literature and patents on H. cordata and its active ingredients published before June 2023 was conducted using PubMed, Google Scholar, Web of Science, and China Knowledge Network. RESULTS: H. cordata is not only edible and medicinal but also used in various aspects of daily life such as fermented beverages, nutraceuticals, feed and cosmetics. The main phytochemical constituents of H. cordata are volatile oils, flavonoids, organic acids and alkaloids. Several in vitro and in vivo studies and clinical trials have found that H. cordata extracts possess antioxidant, anti-inflammatory, antitumor, antibacterial, hepatoprotective and renal, immunomodulatory and potent antiviral effects. The mechanisms of expression of these pharmacological effects are related to the blood-brain barrier, lipophilicity, cAMP signaling and skin permeability, including blocking the MAPK signaling pathway, inhibiting the secretion of inflammatory factors such as TNF-α and IL-1ß, and activating the AMPK pathway. CONCLUSION: This paper provides a comprehensive review of the progress of research on the traditional applications, botany, chemical composition, pharmacological effects and safety of H. cordata and discusses for the first time the economic botanical aspects, which were not explored in the previous reviews. H. cordata has a wide range of bioactive substances whose therapeutic potential has not been fully exploited, and it could provide a new non-toxic approach to many diseases. This traditional medicinal food plant should receive more attention and in-depth research in the future.

A magnetic beads-based ligand fishing method Coupled with UHPLC-QTOF MS for screening and identification of α-glucosidase inhibitors from Houttuynia cordata Thunb.

In this study, a method for the screening and identification of α-glucosidase inhibitors from natural products was developed. The α-glucosidase was immobilized on carboxyl terminated magnetic beads to form a ligand fishing system to screen the potential inhibitors. A total of 9 compounds were fishing out from the crude Houttuynia cordata Thunb. extract. Meanwhile, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) was used for the identification of the chemical structures, including 3 chlorogenic acid isomers, 2 flavone C-glycosides and 4 flavone O-glycosides. The combination of enzyme immobilization magnetic beads and UHPLC-QTOF MS could be used for the screening of bioactive multi-components from herbs with appropriate targets. Taking the advantage of the specificity of enzyme binding and the convenience of magnetic separation, the method has great potential for rapid screening of α-glucosidase inhibitors from complicated natural product extracts.

Houttuynia cordata thunb. alleviates inflammatory bowel disease by modulating intestinal microenvironment: a research review.

Inflammatory bowel disease (IBD) is a complex group of chronic intestinal diseases, the cause of which has not yet been clarified, but it is widely believed that the disorder of the intestinal microenvironment and its related functional changes are key factors in the development of the disease. Houttuynia cordata thunb. is a traditional plant with abundant resources and long history of utilization in China, which has attracted widespread attention in recent years due to its potential in the treatment of IBD. However, its development and utilization are limited owing to the aristolochic acid alkaloids contained in it. Therefore, based on the relationship between the intestinal microenvironment and IBD, this article summarizes the potential mechanisms by which the main active ingredients of Houttuynia cordata thunb., such as volatile oils, polysaccharides, and flavonoids, and related traditional Chinese medicine preparations, such as Xiezhuo Jiedu Formula, alleviate IBD by regulating the intestinal microenvironment. At the same time, combined with current reports, the medicinal and edible safety of Houttuynia cordata thunb. is explained for providing ideas for further research and development of Houttuynia chordate thunb. in IBD disease, more treatment options for IBD patients, and more insights into the therapeutic potential of plants with homology of medicine and food in intestinal diseases, and even more diseases.

Identifying the Potential of miRNAs in Houttuynia cordata-Derived Exosome-Like Nanoparticles Against Respiratory RNA Viruses.

Introduction: Pathogenic respiratory RNA viruses, including influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2, are major causes of causes of acute respiratory infection globally. Plant-derived exosome-like nanoparticles containing miRNAs have shown substantial cross-kingdom regulatory effects on both viral and human transcripts. Houttuynia cordata (H. cordata), a traditional Chinese medicine frequently used to treat respiratory diseases. However, the role of H. cordata-derived exosome-like nanoparticles (HELNs) and the miRNA they encapsulated are unclear. Methods: HELNs were isolated from fresh underground roots (uHELNs) and above ground stems and leaves (aHELNs) using differential centrifugation. The HELNs were identified using transmission electron microscopy, nanoparticle tracking analysis, and zeta potential. Small RNA sequencing and RT-PCR were employed to determine the miRNA expression in uHELNs and aHELNs. All genomes were sourced from the NCBI database. Target prediction of viral genomes was performed using RNAhybrid, while human target prediction was conducted using both RNAhybrid and Miranda. Functional enrichment analysis was applied to the predicted human targets to explore the hub targets and their roles in antiviral effects. The accessibility of miRNA target sites was determined through the MFOLD web server, and customized dual-luciferase reporter assays were administered to validate the computational findings. Results: A total of 12 highly enriched miRNAs were identified in both uHELNs and aHELNs. Upon prediction and verification, miR858a and miR858b were shown to target the NP gene in H1N1, while miR166a-3p targeted the ORF1ab in SARS-CoV-2. However, no valid miRNA targets were found for RSV. Regarding human transcripts, miR168a-3p, miR168b-3p, and miR8175 were found to inhibit MAPK3 expression, and novel_mir2 could suppress both AKT1 and MAPK3 expression. Discussion: This study sheds light on the collaborative antiviral mechanism of miRNAs in HELNs across two species and explores the potential antiviral scopes of both H. cordata miRNAs and HELNs.

RP-HPLC-Based Flavonoid Profiling Accompanied with Multivariate Analysis: An Efficient Approach for Quality Assessment of Houttuynia cordata Thunb Leaves and Their Commercial Products.

Chemical profiling for quality monitoring and evaluation of medicinal plants is gaining attention. This study aims to develop an HPLC method followed by multivariate analysis to obtain HPLC profiles of five specific flavonoids, including rutin (1), hyperin (2), isoquercitrin (3), quercitrin (4), and quercetin (5) from Houttuynia cordata leaves and powder products and assess the quality of H. cordata samples. Eventually, we successfully established HPLC-based flavonoid profiles and quantified the contents of 32 H. cordata fresh leave samples and four powder products. The study also quantified the contents of those five essential flavonoids using an optimized RP-HPLC method. Peak areas of samples were then investigated with principal component analysis (PCA) and hierarchical cluster analysis (HCA) to evaluate the similarity and variance. Principal components in PCA strongly influenced by hyperin and quercetin showed that the samples were clustered into subgroups, demonstrating H. cordata samples' quality. The results of HCA showed the similarity and divided the samples into seven subgroups. In conclusion, we have successfully developed a practical methodology that combined the HPLC-based flavonoid profiling and multivariate analysis for the quantification and quality control of H. cordata samples from fresh leaves and powder products. For further studies, we will consider various environmental factors, including climate and soil factors, to investigate their effects on the flavonoid contents of H. cordata.

Hydroalcoholic root extracts of Houttuynia cordata (Thunb.) standardized by UPLC-Q-TOF-MS/MS promotes apoptosis in human hepatocarcinoma cell HepG2 via GSK-3ß/ß-catenin/PDL-1 axis.

Houttuynia cordata (Thunb.), an important medicinal plant of Northeast India, Korea, and China, is used to treat various ailments and for anticancer research. Knowing its traditional practices, we are interested in the mode-of-action of HCT on HepG2 to co-relate the traditional practice with modern drug therapeutics. UPLC-Q-ToF-Ms analysis of HCT reveals identification of 14 metabolites. Network pharmacology analysis of the 14 compounds showed interaction with 232 different targets with their potential involvement in hepatocellular carcinoma. Whole extracts impart cytotoxicity on variety of cell lines including HepG2. There was a significant morphological alteration in treated HepG2 cells due to impairment of cytoskeletal components like ß and γ- tubulin. Arrest at G1-S checkpoint was clearly indicated downregulation of Cyclin D1. The root extracts actuated apoptosis in HepG2 as evident from altered mitochondrial membrane potential, Annexin V- FITC, BrdU-PI, AO/EtBr assays, and modulations of apoptotic protein expression but without ROS generation. Whole extracts caused abrogation of epithelial to mesenchymal transition with repression of Snail, N-Cadherin, Vimentin, MMP-9, and upregulation of Pan-Cadherin. Pathway analysis found GSK-3ß in Wnt/ß-Catenin signaling cascade to be involved through Hepatocellular carcinoma (hsa05225) pathway. The GSK-3ß/ß-Catenin/PDL-1 signaling was found to be inhibited with the downregulation of pathway components. This was further confirmed by application of EGF, an inducer of the GSK-3ß/ß-Catenin pathway that neutralized the effect of Houttuynia cordata (Thunb.) root extract on the said pathway. Network pharmacology analysis also confirms the synergy network with botanical-bioactive-target-disease which showed Kaempferol to have the highest degree of association with the said pathway.

Targeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata.

Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca2+) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca2+ signaling is a potential therapeutic strategy for asthma. Houttuynia cordata is a traditional Chinese herb that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that H. cordata might modulate intracellular Ca2+ signaling and could help relieve asthmatic airway remodeling. We found that the mRNA and protein levels of inositol trisphosphate receptors (IP3Rs) were elevated in interleukin-stimulated primary human bronchial smooth muscle cells and a house dust mite-sensitized model of asthma. The upregulation of IP3R expression enhanced intracellular Ca2+ release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with H. cordata essential oil rectified the disruption of Ca2+ signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in H. cordata essential oil because we found similar IP3R suppression in response to the commercially available derivative sodium houttuyfonate. An in silico analysis showed that houttuynin, which downregulates IP3R expression, binds to the IP3 binding domain of IP3R and may mediate a direct inhibitory effect. In summary, our findings suggest that H. cordata is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca2+ signaling.

Therapeutic effects on H1N1-induced pneumonia in mice and intestinal bacteria biotransformation of four main flavonoids from Houttuynia cordata Thunb.

Flavonoids widely exist in a large number of Chinese herbal medicines with antiviral and anti-inflammatory properties. Houttuynia cordata Thunb. is a traditional Chinese herbal medicine for heat-clearing and detoxification. In our previous research, total flavonoids from H. cordata (HCTF) effectively alleviated H1N1-induced acute lung injury (ALI) in mice. In this study, 8 flavonoids were recognized from HCTF (containing 63.06 % ± 0.26 % of total flavonoids, as quercitrin equivalents) by UPLC-LTQ-MS/MS. Four main flavonoid glycosides in HCTF (rutin, hyperoside, isoquercitrin and quercitrin) and their common aglycone quercetin (100 mg/kg) all showed therapeutic effects on H1N1-induced ALI in mice. The two flavonoids (hyperoside and quercitrin) with higher contents and quercetin showed stronger therapeutic effects on H1N1-induced ALI in mice. Hyperoside, quercitrin and quercetin significantly reduced the levels of pro-inflammatory factors, chemokines, or neuraminidase activity compared with the same dose of HCTF (p < 0.05). The results of mice intestinal bacteria biotransformation in vitro showed that quercetin was the main metabolite. The conversion rates of hyperoside and quercitrin were significantly higher by the intestinal bacteria under the pathological state (0.81 ± 0.02 and 0.91 ± 0.01, respectively) than normal state (0.18 ± 0.01 and 0.18 ± 0.12, respectively, p < 0.001). Our findings showed that hyperoside and quercitrin were the main efficacious components of HCTF for treating H1N1-induced ALI in mice and could be metabolized to quercetin by intestinal bacteria in pathological state to exert their effects.

Analysis of target organs of Houttuynia cordata: A study on the anti-inflammatory effect of upper respiratory system.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC) is a traditional anti-pyretic herb that is classified as the lung meridian in traditional Chinese medicine. However, no articles have explored the main organs responsible for the anti-inflammatory activities of HC. AIM OF THE STUDY: The aim of the study was to investigate the meridian tropism theory of HC in lipopolysaccharide (LPS)-induced pyretic mice, as well as to identify the underlying mechanisms. MATERIALS AND METHODS: Transgenic mice carrying the luciferase gene driven by nuclear factor-κB (NF-κB) were intraperitoneally injected with LPS and orally administered standardized concentrated HC aqueous extract. The phytochemicals present in the HC extract were analyzed using high-performance liquid chromatography. In vivo and ex vivo luminescent imaging from transgenic mice was used to investigate the meridian tropism theory and anti-inflammatory effects of HC. Microarray analysis of gene expression patterns was used to elucidate the therapeutic mechanisms of HC. RESULTS: HC extract was found to contain phenolic acids, such as protocatechuic acid (4.52%) and chlorogenic acid (8.12%), as well as flavonoids like rutin (2.05%) and quercitrin (7.73%). The bioluminescent intensities induced by LPS in the heart, liver, respiratory system, and kidney were significantly suppressed by HC, while the maximal decrease (about 90% reduction) of induced luminescent intensity was observed in the upper respiratory tract. These data suggested that upper respiratory system might be the target for HC anti-inflammatory abilities. HC affected the processes involved in innate immunity, such as chemokine-mediated signaling pathway, inflammatory response, chemotaxis, neutrophil chemotaxis, and cellular response to interleukin-1 (IL-1). Moreover, HC significantly reduced the proportions of p65-stained cells and the amount of IL-1ß in trachea tissues. CONCLUSION: Bioluminescent imaging coupled with gene expression profile was used to demonstrate the organ selectivity, anti-inflammatory effects, and therapeutic mechanisms of HC. Our data demonstrated for the first time that HC displayed lung meridian-guiding effects and exhibited great anti-inflammatory potential in the upper respiratory tract. The NF-κB and IL-1ß pathways were associated with the anti-inflammatory mechanism of HC against LPS-provoked airway inflammation. Moreover, chlorogenic acid and quercitrin might be involved in the anti-inflammatory properties of HC.

Anti-cancer Effect and Active Phytochemicals of Houttuynia cordata Thunb. against Human Breast Cancer Cells.

BACKGROUND: Houttuynia cordata Thunb (HCT) is a medicinal herb used in Southeast Asia. Aim of this work: This study aimed at investigating the cytotoxicity of this plant extract and fractions towards human breast cancer MDA-MB-231 and MCF-7 cells. HCT's phytoactive compounds are determined. MATERIALS AND METHODS: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mode of cell death was measured by staining with annexin V-FITC and propidium iodide (PI) employing flow cytometry technique. The oxidative stress was measured by using 2',7'-dihydrodichlorofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE+) fluorescent probes and using a fluorescence microplate reader. HCT phytochemicals were characterized by high performance liquid chromatography (HPLC). RESULTS: The proliferation of MDA-MB-231 and MCF-7 cells was dramatically decreased by the crude extract and individual fraction of HCT. Ethyl acetate was the solvent fraction with the highest toxicity against MCF-7 cells, followed by dichloromethane, crude, and hexane fractions, respectively, whereas in MDA-MB231 cells, dichloromethane, crude, hexane, and ethyl acetate fractions each had the strongest impact, respectively. The methanol fraction had no effect on either cell line up to 200 µg/ml. The extract and fractions were less harmful to the NIH3T3 normal murine fibroblast cell line. The mode of both cell death was apoptosis evidenced by the increase of cell population stained with annexin V-FITC and PI. The fluorescence probes of both DCFH-DA and DHE in MDA-MB-231 cell line were enhanced. Phenolic acids included chlorogenic acid (CA), gallic acid (GA), transcoumaric acid (TCA), vanillic acid (VA), and syringic acid (SA), as well as flavonoids like quercetin and rutin, were identified as the active phytochemicals in the crude and fractions by using HPLC method. CONCLUSION: MDA-MB-231cells underwent apoptosis via oxidative stress when induced with HCT hexane fraction. Phenolic acids and flavonoids were identified in HCT's extract and fractions.

Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer's disease model.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by amyloid-ß (Aß) deposition, accompanied by neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, and pus, is revealed to protect neurons from Aß toxicity and regulate cholinergic dysfunction in AD models. In this study, we aimed to investigate the effects of HH on excessive accumulation of Aß followed by neuroinflammation, synaptic degeneration, and memory impairment. Two-month-old 5xFAD transgenic mice were administered HH at 100 mg/kg for 4 months. We observed that HH treatment ameliorated memory impairment and reduced Aß deposits in the brains of the mice. HH directly inhibited Aß aggregation in vitro using the Thioflavin T assay and indirectly suppressed the amyloidogenic pathway by increasing alpha-secretase expression in the mice brain. In addition, HH exerted antineuroinflammatory effects by reducing of glial activation and p38 phosphorylation. Moreover, HH treatment increased the expression of synaptophysin, a presynaptic marker protein. Overall, HH alleviates memory impairment in AD by facilitating nonamyloidogenic pathway and inhibiting neuroinflammation. Therefore, we suggest that HH can be a promising herbal drug for patients with AD requiring multifaceted improvement.

In vitro nephrotoxicity and quantitative UPLC-MS analysis of three aristololactams in Houttuynia cordata.

Three analogues of aristololactam Ⅰ (AL Ⅰ), AL AⅡ, AL FⅠ and AL BⅡ, had been isolated from Houttuynia cordata, a commonly used medicinal and edible plant with heat-removing and toxin-removing functions. Considering the significant nephrotoxicity of AL Ⅰ, this study evaluated the toxicity of these three aristololactams (ALs) on human proximal tubular epithelial cells (HK-2) by MTT assay, ROS assay, ELISA tests and cytologic morphology observation. Furthermore, the distribution of the three ALs in H. cordata were investigated by UPLC-MSn recognition and quantitation in SIM mode, so as to estimate primarily the safety of the plant. The results showed that all the three ALs in H. cordata had comparative cytotoxicity as AL I with the IC50 values from 3.88 µM to 20.63 µM, caused high levels of cellular levels of reactive oxygen species (ROS) in HK-2 cells, exhibited the potential to cause renal fibrosis by remarkably increasing the levels of transforming growth factor-ß (TGF-ß1) and fibronectin (FN), and induced fibrous changes in morphology of HK-2 cells. The contents of the three ALs varied significantly in 30 batches of H. cordata from different regions and parts. Overall, the aerial part contained much more ALs (3.20 - 108.19 µg/g) than the underground part (0.95 - 11.66 µg/g), and flowers had the highest contents. Besides, no ALs were detected in the water extract of any part of H. cordata. This work revealed that the aristololactams in H. cordata had similar in vitro nephrotoxicity as AL Ⅰ and were mainly distributed in the aerial part of the plant.

Sodium houttuyfonate derived from Houttuynia cordata Thunb improves intestinal malfunction via maintaining gut microflora stability in Candida albicans overgrowth aggravated ulcerative colitis.

Candida albicans is a common opportunistic pathogen and normally resides in the human gut. Increasing number of reports link the overgrowth of C. albicans to the severity of ulcerative colitis (UC). Sodium houttuyfonate (SH), a derivative of the medicinal herb Houttuynia cordata Thunb, has been demonstrated to exhibit decent antifungal and anti-inflammatory activities. We showed previously that SH could ameliorate colitis mice infected with C. albicans. However, it is unclear whether the therapeutic effect of SH is connected to its modulation of intestinal microflora in UC. In this study, the impact of SH on the gut microbiota was explored in both cohabitation and non-cohabitation patterns. The results showed that in UC mice inflicted by C. albicans, the administration of SH could greatly improve the pathological signs, weaken the oxidative stress and inflammatory response, and enhance the intestinal mucosal integrity. By 16S rRNA gene sequencing, we found that C. albicans interference caused intestinal microbiota dysbiosis accompanied by an increase of some harmful pathogens including Klebsiella and Bacteroides. In contrast, SH could modulate the abundance and diversity of microbiota with an increase of several beneficial bacteria comprising short-chain fatty acid-producing bacteria (Lachnospiraceae_NK4A136_group, Intestinimonas) and probiotics (Lactobacillus and Alloprevotella). Furthermore, the cohabitation strategy could also prove the efficacy of SH, indicating a role of transmissible gut flora in the colitis model. These findings suggest that SH might be an effective compound for the treatment of UC complicated by C. albicans overgrowth through maintaining gut microbiota homeostasis, thereby improving intestinal function.

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology.

Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

The synergistic effect and mechanisms of flavonoids and polysaccharides from Houttuynia cordata on H1N1-induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia. AIM OF THE STUDY: The purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying. MATERIALS AND METHODS: HCF or HCP were administrated separately or combined in different proportions on influenza virus H1N1 - infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blot, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissues. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestines. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis. RESULTS: In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by HCF and HCP combination reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediators. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury. The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema. CONCLUSIONS: Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.

Protective Effects of Fermented Houttuynia cordata Against UVA and H2O2-Induced Oxidative Stress in Human Skin Keratinocytes.

The biological activities of Houttuynia cordata (H. cordata) fermented with Aureobasidium pullulans (A. pullulans) was investigated for human skin keratinocyte-induced chemical and photo oxidations. In this research, H2O2/UVA-induced HaCaT cell lines were treated with H. cordata water/ethanol extracts (HCW/HCE) and fermented with A. pullulans water/ethanol extracts (HCFW/HCFE). A. pullulans fermented with H. cordata (HCFW) increased in 5.4-folds of total polyphenol (HCFW 46.89 mg GAE/extract g), and 2.3-folds in flavonoids (HCFW 53.80 mg GAE/extract g) compared with water extracts of H. cordata (HCW). Further, no significant cytotoxicity for HaCaT cells showed by all the extracts of H. cordata fermented with A. pullulans. HCFW extracts have significantly lowered inflammation factors such as COX-2 and Hsp70 proteins in oxidative stressed HaCaT cells induced by H2O2 and UVA treatments. All H. cordata extracts significantly downregulated gene expression involved in oxidative stress and inflammation factors, including IL-1ß, IL-6, COX-2, TNF-α, NF-κB, and MMP-1 in the H2O2/UVA-treated HaCaT cells. However, keratin-1 gene expression in the UVA-treated HaCaT cells was increased in twofolds by HCFW extracts. Further, A. pullulans fermented H. cordata extracts (HCFW/HCFE) reduced the genes involved in oxidative stresses more effectively than those of H. cordata extract only. Overall, the polyphenol-rich extracts of H. cordata fermented with A. pullulans showed synergistic protective effects for human epidermal keratinocytes to prevent photoaging and intrinsic aging by anti-oxidation and anti-inflammatory functions.

Analysis of Volatile Compounds from Different Parts of Houttuynia cordata Thunb.

Houttuynia cordata Thunb. is a medicinal and edible plant that has been commonly used in traditional Chinese medicine since ancient times. This study used headspace solid-phase microextraction (HS-SPME) and direct injection, combined with gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS), to identify the volatile compounds in H. cordata. Extraction from different parts of the plant using different extraction techniques for the identification of volatile compounds were determined. A total of 93 volatile components were analyzed in the leaves, stems, rhizomes, and whole plant samples of H. cordata. The leaves contained more (Z)-3-hexenal, ß-myrcene, (Z)-ß-ocimene, and (4E,6E)-allo-ocimene; the stems contained more geranyl acetate and nerolidol; and rhizomes contained more α-pinene, ß-pinene, limonene, 2-undecanone, and decanoyl acetaldehyde. Among them, the essential oil extracted by HS-SPME could produce more monoterpenes, while direct injection could obtain higher contents of aliphatic ketones, terpene esters, sesquiterpenes, and was more conducive to the extraction of 2-undecanone and decanoyl acetaldehyde.