In Silico Screening of Potential Phytocompounds from Several Herbs against SARS-CoV-2 Indian Delta Variant B.1.617.2 to Inhibit the Spike Glycoprotein Trimer

In October 2020, the SARS-CoV-2 B.1.617 lineage was discovered in India. It has since become a prominent variant in several Indian regions and 156 countries, including the United States of America. The lineage B.1.617.2 is termed the delta variant, harboring diverse spike mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD), which may heighten its immune evasion potentiality and cause it to be more transmissible than other variants. As a result, it has sparked substantial scientific investigation into the development of effective vaccinations and anti-viral drugs. Several efforts have been made to examine ancient medicinal herbs known for their health benefits and immune-boosting action against SARS-CoV-2, including repurposing existing FDA-approved anti-viral drugs. No efficient anti-viral drugs are available against the SARS-CoV-2 Indian delta variant B.1.617.2. In this study, efforts were made to shed light on the potential of 603 phytocompounds from 22 plant species to inhibit the Indian delta variant B.1.617.2. We also compared these compounds with the standard drug ceftriaxone, which was already suggested as a beneficial drug in COVID-19 treatment; these compounds were compared with other FDA-approved drugs: remdesivir, chloroquine, hydroxy-chloroquine, lopinavir, and ritonavir. From the analysis, the identified phytocompounds acteoside (−7.3 kcal/mol) and verbascoside (−7.1 kcal/mol), from the plants Clerodendrum serratum and Houttuynia cordata, evidenced a strong inhibitory effect against the mutated NTD (MT-NTD). In addition, the phytocompounds kanzonol V (−6.8 kcal/mol), progeldanamycin (−6.4 kcal/mol), and rhodoxanthin (−7.5 kcal/mol), from the plant Houttuynia cordata, manifested significant prohibition against RBD. Nevertheless, the standard drug, ceftriaxone, signals less inhibitory effect against MT-NTD and RBD with binding affinities of −6.3 kcal/mol and −6.5 kcal/mol, respectively. In this study, we also emphasized the pharmacological properties of the plants, which contain the screened phytocompounds. Our research could be used as a lead for future drug design to develop anti-viral drugs, as well as for preening the Siddha formulation to control the Indian delta variant B.1.617.2 and other future SARS-CoV-2 variants.

Topical Application of Houttuynia Cordata Thunb Ethanol Extracts Increases Tumor Infiltrating CD8+/Treg Cells Ratio and Inhibits Cutaneous Squamous Cell Carcinoma In Vivo

Houttuynia cordata Thunb (HCT) is a medicinal and edible herb which has beneficial effects on various diseases due to its diuretic, anti-inflammatory, anti-oxidative, anti-microbial, anti-viral, anti-cancer and anti-diabetic properties. Most of reports of its anti-cancer activity were conducted in vitro, and its effects on cutaneous squamous cell carcinoma (SCC) has not been investigated yet. Using DMBA/TPA induced SCC mice model, we found that topical treatment by HCT, as well as its bioactive ingredient monomer, efficiently inhibited tumor growth. Mechanistically, we found tumor infiltrating CD4+, Foxp3+ T regulatory cells (Tregs) were significantly reduced and CD8+/Treg cells ratio was largely increased in tumors after HCT treatment. In addition, several chemokines which recruited immune cells were largely reduced when SCC cancer cells were treated by HCT in vitro. Our results demonstrate the therapeutic effects of HCT on cutaneous SCC and indicate it might inhibit cancer through regulating tumor infiltrating lymphocytes and the tumor immune microenvironments.

Estimation of Quercetin and Rutin Content in Hyouttunia cordata and Centella asiatica Plant Extracts Using UV-Spectrophotometer

Flavonoids are secondary plant metabolites normally found as pigmented compounds in plants. Quercetin and rutin are two important and commonly found flavonoids in nature and exhibit wide pharmacological effects such as antioxidant, anticarcinogenic, antiviral, anti-inflammatory, antidiabetic, and hepatoprotective activities as well as antimicrobial activity. In this study, quercetin and rutin content is being quantified in the plant extracts of Centella asiatica and Houttuynia cordata and considerable amounts of these two flavonoids were depicted. A single beam UV – Spectrophotometer was used to measure the absorbance of the standard as well as test solutions. Calibration curves were constructed for standard quercetin and rutin in such a way that x-axis denotes concentration and the y-axis denotes the absorbance. The calibration curves showed linearity at concentrations 5-25 ?g /ml of quercetin and rutin respectively with a good correlation coefficient (r) of 0.99 for both the curves. The absorbance of the two test extracts was obtained from the calibration curve and respective concentrations of quercetin and rutin for the two extracts were calculated. The amount of quercetin and rutin present was expressed as Total Flavonoid Content (TFC) i.e. the amount of the flavonoid in ?g present per mg of the respective plant extract. The quercetin content in both the plant extracts was found to be more (315.8 in Houttuynia cordata; 487.6 in Centella asiatica) than the content of rutin (152.2 in Houttuynia cordata; 171.0 in Centella asiatica).

Effects of temperatures on growth, physiological, and antioxidant characteristics in Houttuynia cordata

Houttuynia cordata Thunb. (HC) is a traditional medicinal plant with a variety of pharmaceutical activities. The objective of this study was to investigate the growth, photosynthetic parameters, and antioxidant properties of HC plants in response to various temperatures. Pots of HC plants were maintained in day/night temperatures of 15/10 °C, 20/15 °C, 25/20 °C (control), 30/25 °C, and 35/30 °C for two months in each of five growth chambers having a 13.5 h photoperiod at 396, 432, 474, 449, and 619 µmol·m-2·s-1 radiation, respectively. Eight plants for each temperature were randomly placed in a growth chamber. HC plants survived at 30/25 °C and 35/30 °C treatments and had significantly higher plant heights, leaf numbers, and soil-plant analysis development (SPAD) and normalized difference vegetation index (NDVI) values compared to other treatments. However, long-term 35/30 °C treatment caused reductions in leaf length and width, significantly decreasing shoot and leaf fresh weight (FW) and dry weight (DW) compared to 30/25 °C treatment and controls. These results indicate that HC leaf development was affected during the 35/30 °C treatment, and that both SPAD and NDVI can help in advancing our understanding of the photosynthesis process in HC. Moreover, all plants subjected to 15/10 °C suffered more severely in all traits and parameters than other treatments. Therefore, HC plants tended to be heat-tolerant and exhibited adaptive morphologic plasticity to 30/25 °C conditions. Positive and significant correlations were observed among temperatures and total phenolics (TP), total flavonoids (TF), chlorogenic acid (CGA), and hyperoside (HO) content, and all bioactive contents increased as temperature increased, except that both CGA and HO content were remarkably decreased after 30/25 °C treatment. Thus, 30/25 °C treatment would be more beneficial for high marketability resulting from increased leaf number, DW, and all secondary metabolites compared to other treatments, and for use as a health food and for medicinal purposes. In addition, leaf growth, physiological parameters, and secondary metabolite accumulations in HC plants can be optimized for commercial production via temperature control technologies. This approach may also be applicable to leafy vegetables to produce stable industrial supplies having high leaf yields and metabolite content.

Photoprotective Effects of a Hyperoside-Enriched Fraction Prepared from Houttuynia cordata Thunb. on Ultraviolet B-Induced Skin Aging in Human Fibroblasts through the MAPK Signaling Pathway

Ultraviolet-B (UVB) irradiation causes skin damage via deleterious effects including oxidative stress, inflammation, and collagen degradation. The photoprotective effects of a hyperoside-enriched fraction obtained from Houttuynia cordata Thunb. (H. cordata) on the attenuation of UVB-induced skin aging in human fibroblasts were investigated. The solvent-partition technique was used to establish the hyperoside-enriched fraction of H. cordata (HcEA). The active compounds identified in the H. cordata extracts were hyperoside, quercitrin, chlorogenic acid, and rutin. With regard to the photoprotective effects of H. cordata on UVB-irradiated dermal fibroblasts, HcEA and hyperoside inhibited intracellular ROS production and inflammatory cytokine secretions (IL-6 and IL-8), while increasing collagen type I synthesis along with downregulating MMP-1 gene and protein expressions. Mechanistically, the hyperoside-enriched fraction obtained from H. cordata inhibited UVB-irradiated skin aging through regulation of the MAPK signaling pathway by attenuating the activation of JNK/ERK/c-Jun in human dermal fibroblasts. The hyperoside-enriched fraction of H. cordata exerted potent anti-skin aging properties against UVB exposure. The findings of this study can be applied in the cosmetics industry, as H. cordata extract can potentially be used in pharmaceutical or cosmetic formulations as a photoprotective or anti-skin aging agent.

A Review on the Anti-Viral Activity of Houttuynia cordata: A Possible Herb for the Management and Treatment of COVID-19

Plants are an important source of natural products and they play a vital role in the field of medicinal chemistry and pharmaceutical science. Traditional medicines have been practiced and used for thousands of years, mostly in Asian countries, where plants are the main sources of medicine. Houttuynia cordata, a herb that belongs to the family Saururaceae, has a wide range of pharmacological activities and is used traditionally in conditions like anisolobis sores, heatstroke, lung carbuncles, malaria, scrotal abscess, tonsillitis, salammoniac poison and has also been widely accepted to possess anti-cancer, anti-oxidant, anti-hypertension, anti-inflammatory, anti-mutagenic, antibacterial, anti-viral and anti-purulent activity. Moreover, it is one of the herbs that was recognized during pandemic outbreaks, such as Severe Acute Respiratory Syndrome Coronavirus (SARS CoV) in China, virulent Newcastle Disease Virus (VNDV) in Java (Indonesia) and Newcastle (England). In this review, we briefly discuss the role of H. cordata as an anti-viral agent and the possibility of developing a dosage form against Coronavirus disease-19 (COVID-19).

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Houttuynia cordata Thunb. in Pulmonary Fibrosis via Network Pharmacology Analysis

Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. Houttuynia cordata Thunb. (family: Saururaceae) (H. cordata), as has been reported, is a Chinese herbal medicine commonly used to treat upper respiratory tract infection and bronchitis. Our previous study has proven that sodium houttuyfonate (an additional compound from sodium bisulfite and houttuynin) had beneficial effects in the prevention of pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. In the present study, network pharmacology was used to investigate the efficiency and potential mechanisms of H. cordata in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of H. cordata species were screened. Then, the prediction of the potential active ingredients, action targets, and signaling pathways were conducted through the Gene Ontology (GO), protein–protein interaction (PPI),and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results of network pharmacology prediction suggested that H. cordata may act through multiple signaling pathways to alleviate PF, including the phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) pathways, mitogen-activated protein kinase (MAPK) pathways, the tumor necrosis factor (TNF) pathways, and interleukin-17 (IL-17) signaling pathways. Molecular docking experiments showed that the chemical constituents of H. cordata had good affinity with TNF, MAPK1, and AKT1, and using lipopolysaccharide (LPS)-induced A549 cells, a model was established to verify the anti-pulmonary fibrosis effects and related mechanisms of H. cordata–relevant constituents. Finally, these evidences collectively suggest H. cordata may alleviate PF progression via PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of H. cordata in the treatment of PF.