Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II.

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies.

Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure-activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC50: 48.73 ± 7.59 µM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.

The investigation of hawthorn (Crataegus orientalis) plant's inhibition effect on angiotensin converting enzyme and in silico studies.

Hawthorn plant is used among people due to its cardiovascular, anti-inflammatory, and antihistamine properties. But no scientific study has been done about Crataegus orientalis (Mill.) M.Bieb. The presented study was planned to determine the effects of ethanol and n-hexane extracts of Crataegus orientalis leaves on human plasma ACE enzyme. In the study, the effect of plant extracts on ACE was studied by the spectrophotometric method. The chemical composition of the plant extracts was determined by HPLC-DAD analyses. In addition, molecular doking and ADME prediction studies were carried out. As a result, the obtained data showed that Crataegus orientalis could have an important place in the pharmaceutical industry and drug discovery studies, as it supports the traditional use of Crataegus orientalis as hypotensive. The results of the molecular docking studies revealed that the interactions of the selected compounds with the human ACE enzyme caused inhibition.

Raman spectroscopy study of 7,8-dihydrofolate inhibition on the Wuhan strain SARS-CoV-2 binding to human ACE2 receptor.

Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections.

Chemical Compositions of Scutellaria baicalensis Georgi. (Huangqin) Extracts and Their Effects on ACE2 Binding of SARS-CoV-2 Spike Protein, ACE2 Activity, and Free Radicals.

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals. A total of 76 compounds were tentatively identified from the extracts. The water extract showed a greater inhibition on the interaction between SARS-CoV-2 spike protein and ACE2, but less inhibition on ACE2 activity than that of the ethanol extract on a per botanical weight concentration basis. The total phenolic content was 65.27 mg gallic acid equivalent (GAE)/g dry botanical and the scavenging capacities against HO●, DPPH●, and ABTS●+ were 1369.39, 334.37, and 533.66 µmol trolox equivalent (TE)/g dry botanical for the water extract, respectively. These values were greater than those of the ethanol extract, with a TPC of 20.34 mg GAE/g, and 217.17, 10.93, and 50.21 µmol TE/g against HO●, DPPH●, and ABTS●+, respectively. The results suggested the potential use of huangqin as a functional food ingredient in preventing COVID-19.

Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Evaluation of antihypertensive activity and molecular docking analysis of Padina boergesenii extract.

INTRODUCTION: Antihypertensive drugs that are chemically synthesized usually tend to initiate different health complications. The quest for bioactive molecules to create novel medicines has focused on Marine resources like seaweeds. These molecules can furnish a positive probability for patients to gain benefits from these natural substances. METHODS: This study aims to identify phytoconstituents present in brown seaweed-Padina boergesenii. Five different solvents were used to prepare extracts and their antioxidant activity as well as antihypertensive activity was evaluated. Phytoconstituents were identified using LC-MS/MS, and subjected to molecular interaction against ACE enzyme. RESULTS: The 70% ethanolic extract exhibited the highest total phenolic content (TPC), significant radical scavenging activity and concentration dependent Angiotensin Converting Enzyme (ACE) inhibition activity. LC-MS/MS analysis confirmed the presence of bioactive compounds from which 7,8 dihydroxycoumarin had the highest affinity against ACE enzyme in molecular docking study. CONCLUSION: These findings advocate that Padina boergesenii can be a potential source for developing novel antihypertensive therapeutic drug(s) and could pave the way for evolving effective and safe remedies from natural resources.

Flavonoids derived from medicinal plants as a COVID-19 treatment.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell's receptor protein. The COVID-19 pandemic had a profound impact on global public health and economies. Although various effective vaccinations and medications are now available to prevent and treat COVID-19, natural compounds derived from medicinal plants, particularly flavonoids, demonstrated therapeutic potential to treat COVID-19 disease. Flavonoids exhibit dual antiviral mechanisms: direct interference with viral invasion and inhibition of replication. Specifically, they target key viral molecules, particularly viral proteases, involved in infection. These compounds showcase significant immunomodulatory and anti-inflammatory properties, effectively inhibiting various inflammatory cytokines. Additionally, emerging evidence supports the potential of flavonoids to mitigate the progression of COVID-19 in individuals with obesity by positively influencing lipid metabolism. This review aims to elucidate the molecular structure of SARS-CoV-2 and the underlying mechanism of action of flavonoids on the virus. This study evaluates the potential anti-SARS-CoV-2 properties exhibited by flavonoid compounds, with a specific interest in their structure and mechanisms of action, as therapeutic applications for the prevention and treatment of COVID-19. Nevertheless, a significant portion of existing knowledge is based on theoretical frameworks and findings derived from in vitro investigations. Further research is required to better assess the effectiveness of flavonoids in combating SARS-CoV-2, with a particular emphasis on in vivo and clinical investigations.

Inhibition of multiple SARS-CoV-2 variants entry by Lycium barbarum L. polysaccharides through disruption of spike protein-ACE2 interaction.

Viral respiratory infections are major human health concerns. The most striking epidemic disease, COVID-19 is still on going with the emergence of fast mutations and drug resistance of pathogens. A few polysaccharide macromolecules from traditional Chinese medicine (TCM) have been found to have direct anti-SARS-CoV-2 activity but the mechanism remains unclear. In this study, we evaluated the entry inhibition effect of Lycium barbarum polysaccharides (LBP) in vitro and in vivo. We found LBP effectively suppressed multiple SARS-CoV-2 variants entry and protected K18-hACE2 mice from invasion with Omicron pseudovirus (PsV). Moreover, we found LBP interfered with early entry events during infection in time-of-addition (TOA) assay and SEM observation. Further surface plasmon resonance (SPR) study revealed the dual binding of LBP with Spike protein and ACE2, which resulted in the disruption of Spike-ACE2 interaction and subsequently triggered membrane fusion. Therefore, LBP may act as broad-spectrum inhibitors of virus entry and nasal mucosal protective agent against newly emerging respiratory viruses, especially SARS-CoV-2.

Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19.

Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.

Hippophae rhamnoides Prevents Oleic Acid-Induced Acute Respiratory Distress Syndrome by Releasing Acetylcholinesterase Activity and Mitigation of Angiotensin-Converting Enzyme Level.

Hippophae rhamnoides exhibit a wide variety of medicinal and pharmacological effects. The present study aims to determine the role of ethanol extract of H. rhamnoides on oleic acid (OA)-induced acute respiratory distress syndrome (ARDS) in rats. Male rats were randomly divided into the following groups: (I) Control, (II) OA, and (III) OA+H. rhamnoides. H. rhamnoides extract (500 mg/kg) was given orally for 2 weeks before OA in Group III. Levels of total antioxidant capacity, total oxidant status (TOS), myeloperoxidase (MPO), mitogen-activated protein kinase (MAPK), acetylcholinesterase (AChE), and angiotensin-converting enzyme (ACE) were quantified by enzyme-linked immunosorbent assay (ELISA). Real time quantitative polymerase chain reaction was utilized to evaluate the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and matrix metalloproteinase 2 (MMP2). Also, Caspase-3 immunostaining and expression were performed to evaluate apoptosis. Compared with the OA group, there was a significantly decrease in the levels of MPO, TOS, MAPK, and ACE and in the expression of NF-κB, TNF-α, IL-6, MMP2, and Caspase-3 in the H. rhamnoides administration group. Moreover, the activity of AChE and level of TAS were substantially higher in the H. rhamnoides administration compared with the OA group. The findings in the study suggest that the protective effect of H. rhamnoides pretreatment may act through inhibition of the ACE activity, releasing AChE, regulation of inflammatory cytokine levels, and suppression of apoptotic process in ARDS.

Nigella sativa and its chemical constituents: pre-clinical and clinical evidence for their potential anti-SARS-CoV-2 effects.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 500 million reported cases of COVID-19 worldwide with relatively high morbidity and mortality. Although global vaccination drive has helped control the pandemic, the newer variant of the virus still holds the world in ransom. Several medicinal herbs with antiviral properties have been reported, and one such promising herb is Nigella sativa (NS). Recent molecular docking, pre-clinical, and clinical studies have shown that NS extracts may have the potential to prevent the entry of coronaviruses into the host cell as well as to treat and manage COVID-19 symptoms. Several active compounds from NS, such as nigelledine, α-hederin, dithymoquinone (DTQ), and thymoquinone (TQ), have been proposed as excellent ligands to target angiotensin-converting enzyme 2 (ACE2 receptors) and other targets on host cells as well as the spike protein (S protein) on SARS-CoV-2. By binding to these target proteins, these ligands could potentially prevent the binding between ACE2 and S protein. Though several articles have been published on the promising therapeutic role of NS and its constituents against SARS-CoV-2 infection, in this review, we consolidate the published information on NS and SARS-CoV-2, focusing on pre-clinical in silico studies as well as clinical trials reported between 2012 and 2023.

Angiotensin-converting enzyme inhibitory peptide IVGFPAYGH protects against liver injury in mice fed a high­sodium diet by inhibiting the RAS and remodeling gut microbial communities.

Consuming a high­sodium diet carries serious health risks and significantly influences the activation state of the renin-angiotensin system (RAS). This study evaluates the protective effect of angiotensin-converting enzyme (ACE) inhibitory peptide IVGFPAYGH on a high­sodium diet-induced liver injury. IVGFPAYGH supplementation increased the activities of liver antioxidase and decreased the levels of liver inflammatory factor in mice fed a high­sodium diet (8 % NaCl). IVGFPAYGH supplementation also reduced liver fatty acid synthesis and promoted fatty acid oxidation, increased the expression of low-density lipoprotein receptor, and improved liver dyslipidemia. Furthermore, IVGFPAYGH supplementation inhibited the activation of the liver RAS via inhibiting ACE activity and reducing angiotensin II levels in mice fed a high­sodium diet. Moreover, IVGFPAYGH supplementation could alter the gut microbiota composition toward a normal gut microbiota composition and increase the abundance of the Lactobacillus genus. IVGFPAYGH supplementation also increased the expression levels of small intestinal tight junction protein and cecum short-chain fatty acids. Thus, IVGFPAYGH supplementation may maintain intestinal homeostasis and improve high­sodium diet-induced liver injury by altering the gut microbiota composition and inhibiting the RAS. IVGFPAYGH is a promising functional ingredient for protecting liver damage caused by a high­sodium diet.

Study of the Antihypertensive Effect of Scorzonera undulata ssp. deliciosa in Albino Wistar Rats.

AIMS: The study aimed to investigate the antihypertensive activity of Scorzonera undulata ssp. deliciosa. BACKGROUND: Scorzonera undulata ssp deliciosa, locally known as "Guiz", is used in traditional medicine in Morocco as a diuretic and mainly against snake bites. OBJECTIVE: This study investigated the possible antihypertensive effect of the aqueous extract of Scorzonera undulata (AESU). MATERIAL AND METHODS: In the present study, the antihypertensive activity of AESU AUSU was tested in normotensive and hypertensive rats. RESULTS: The results indicated that AESU decreased the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. The data revealed that AESU exerted its antihypertensive effect through vasodilatory properties. Interestingly, the study demonstrated that the vasorelaxation ability of AESU might be mediated through receptor-operated calcium channels (ROCCs). However, AESU dhad effect on inhibiting ACE-2. CONCLUSION: The present study indicates the antihypertensive and vasorelaxant activities of AESU in hypertensive rats.

Potential Antihypertensive Activity of the Aqueous Extract of Ammi visnaga and its Effect on ACE-2 in Rats.

AIMS: This work aimed to investigate the antihypertensive activity of Ammi visnaga. BACKGROUND: The aqueous extract of Ammi visnaga has traditionally been used to treat hypertension in Morocco. OBJECTIVE: The objective of this investigation was to evaluate the effect of Ammi visnaga aqueous extract (AVAE) on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of Ammi visnaga on vasodilatation was assessed in isolated rat aortic rings with functional endothelium pre-contracted with epinephrine EP or KCl. METHODS: AVAE was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received oral AVAE at two selected doses of 70 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. RESULTS: AVAE lowered blood pressure only in L-Name-induced hypertensive rats. Furthermore, AVAE (0.375-1.375 mg/ml) showed a vasodilator effect in isolated aortic rats. In addition, not all of the medications used in our study were responsible for the signaling pathway. As a result, additional pharmaceuticals are required to confirm the mechanism of this signaling pathway. CONCLUSION: The aqueous extract of Ammi visnaga exerts an interesting antihypertensive activity, which could be mediated through its vasorelaxant activity. The study supports its use as a medicinal plant against hypertension in Morocco.

Dauricine interferes with SARS-CoV-2 variants infection by blocking the interface between RBD and ACE2.

The continued viral evolution results in the emergence of various SARS-CoV-2 variants, such as delta or omicron, that are partially resistant to current vaccines and antiviral medicines, posing an increased risk to global public health and raising the importance of continuous development of antiviral medicines. Inhibitor screening targeting the interactions between the viral spike proteins and their human receptor ACE2 represents a promising approach for drug discovery. Here, we demonstrate that the evolutionary trend of the SARS-CoV-2 variants is associated with increased electrostatic interactions between S proteins and ACE2. Virtual screening based on the ACE2-RBD binding interface identified nine monomers of Traditional Chinese medicine (TCM). Furthermore, live-virus neutralization assays revealed that Dauricine, one of the identified monomers, exhibited an antiviral activity with an IC50 range of 18.2 to 33.3 µM for original strain, Delta, and Omicron strains, respectively. The computational study showed that the polycyclic and methoxy groups of Dauricine adhere to the RBD surface through π-π and electrostatic interactions. The discovery of Dauricine is a successful attempt to target viral entry, which will not only help society to respond quickly to viral variants, but also accelerate variant drug development thereby reducing the pressure on health authorities to respond to outbreaks.

Anisomeles indica Extracts and Their Constituents Suppress the Protein Expression of ACE2 and TMPRSS2 In Vivo and In Vitro.

Coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. This highly contagious pneumonia remains a significant ongoing threat. Uncertainties persist about the virus's effects on human health, underscoring the need for treatments and prevention. Current research highlights angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key targets against SARS-CoV-2. The virus relies on ACE2 to enter cells and TMPRSS2 to activate its spike protein. Inhibiting ACE2 and TMPRSS2 expression can help prevent and treat SARS-CoV-2 infections. Anisomeles indica (L.) Kuntze, a medicinal plant in traditional Chinese medicine, shows various promising pharmacological properties. In this study, ethanolic extracts of A. indica were examined both in vivo (250 and 500 µM) and in vitro (500 µM). Through Western blotting analysis, a significant reduction in the expression levels of ACE2 and TMPRSS2 proteins was observed in HepG2 (human hepatocellular carcinoma) cells and HEK 293T (human embryonic kidney) cell lines without inducing cellular damage. The principal constituents of A. indica, namely, ovatodiolide (5 and 10 µM), anisomlic acid (5 and 10 µM), and apigenin (12.5 and 25 µM), were also found to produce the same effect. Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.

In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K.

SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor for viral entry, while TMPRSS2 proteolytically cleaves the S protein into S1 and S2 subunits, promoting membrane fusion. Therefore, ACE-2 and TMPRSS2 are potential drug targets for treating COVID-19, and their inhibition is a promising strategy for treatment and prevention. This study proposes that ginsenoside compound K (G-CK), a triterpenoid saponin abundant in Panax Ginseng, a dietary and medicinal herb highly consumed in Korea and China, effectively binds to and inhibits ACE-2 and TMPRSS2 expression. We initially conducted an in-silico evaluation where G-CK showed a high affinity for the binding sites of the two target proteins of SARS-CoV-2. Additionally, we evaluated the stability of G-CK using molecular dynamics (MD) simulations for 100 ns, followed by MM-PBSA calculations. The MD simulations and free energy calculations revealed that G-CK has stable and favorable energies, leading to strong binding with the targets. Furthermore, G-CK suppressed ACE2 and TMPRSS2 mRNA expression in A549, Caco-2, and MCF7 cells at a concentration of 12.5 µg/mL and in LPS-induced RAW 264.7 cells at a concentration of 6.5 µg/mL, without significant cytotoxicity.ACE2 and TMPRSS2 expression were significantly lower in A549 and RAW 264.7 cells following G-CK treatment. These findings suggest that G-CK may evolve as a promising therapeutic against COVID-19.

Antibacterial and Angiotensin I-Converting Enzyme (ACE) Inhibition Activities of Essential Oil from Java Cardamom (Amomum compactum) Fruit.

The essential oil has been reported to be one of the Angiotensin I-Converting Enzyme (ACE) inhibitor resources. Moreover, it has been proven against bacterial pathogens that cause infectious diseases. Amomum compactum is one source of essential oil, known as Javanese cardamom is a spice herb commonly used for flavouring food and traditional medicine in Indonesia. However, ACE inhibition activity of A. compactum has not been reported. The purposes of this study were to identify the main constituent of volatile compounds, inhibition activity toward bacteria, and antihypertension potency of A. compactum essential oils. Volatile compounds were investigated using Gas Chromatography-Mass Spectrometry (GC-MS). The antimicrobial activity was observed using the microdilution method toward Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. The antihypertension effect was studied using an ACE inhibition assay. The result showed that eucalyptol was a primary compound of A. compactum fruit either in Banjar (BJR) and Bogor (BGR) essential oils with the value of 62.22% and 66.23%, respectively. Both BJR and BGR are more active to inhibit gram-positive bacteria (B. subtilis) with MIC values of 1 mg/mL. Meanwhile, the BJR exhibited a higher inhibitory activity effect toward ACE compared to BGR with the value of IC50 64.86 ± 0.57 µg/mL. These findings suggest that A. compactum essential oil can be the potential to lead to the treatment of hypertension as an ACE inhibitor and antibacterial agent. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01080-x.