Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.

The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein-protein interactions, we also chose a collection of well-known functional protein partners for pleckstrin. Investigations were also carried out on the relationship between pleckstrins and other cancers regarding mutations and copy number alterations. The cumulative impact of pleckstrin and their associated genes on various cancers, Gene Ontology (GO), and pathway analyses were used for their evaluation. Thus, the expression profiles of PHLDA family members and their prognosis in various cancers may be revealed by this study. During this multiomics analysis, we found that among the PHLDA family, PHLDA1 may be a therapeutic target for several cancers, including kidney, colon, and brain cancer, while PHLDA2 can be a therapeutic target for cancers of the colon, esophagus, and pancreas. Additionally, PHLDA3 may be a useful therapeutic target for ovarian, renal, and gastric cancer.

In Silico and In Vitro Study of Isoquercitrin against Kidney Cancer and Inflammation by Triggering Potential Gene Targets.

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-ß-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, cytotoxicity assay, and RT-PCR and qRT-PCR validation. According to the MD simulation (250 ns), we found that IGF1R, PIK3CA, and PTGS2, except for IL6 gene targets, show stable binding energy with a stable complex with isoquercitrin. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the final targets to determine their regulatory functions and signaling pathways. Furthermore, we checked the cytotoxicity effect of isoquercitrin (IQ) and found that 5 µg/mL and 10 µg/mL doses showed higher cell viability in a normal kidney cell line (HEK 293) and also inversely showed an inhibition of cell growth at 35% and 45%, respectively, in the kidney cancer cell line (A498). Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation.

Butyrate's (a short-chain fatty acid) microbial synthesis, absorption, and preventive roles against colorectal and lung cancer.

Butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, is a source of energy for colonocytes. Butyrate is essential for improving gastrointestinal (GI) health since it helps colonocyte function, reduces inflammation, preserves the gut barrier, and fosters a balanced microbiome. Human colonic butyrate producers are Gram-positive firmicutes, which are phylogenetically varied. The two most prevalent subgroups are associated with Eubacterium rectale/Roseburia spp. and Faecalibacterium prausnitzii. Now, the mechanism for the production of butyrate from microbes is a very vital topic to know. In the present study, we discuss the genes encoding the core of the butyrate synthesis pathway and also discuss the butyryl-CoA:acetate CoA-transferase, instead of butyrate kinase, which usually appears to be the enzyme that completes the process. Recently, butyrate-producing microbes have been genetically modified by researchers to increase butyrate synthesis from microbes. The activity of butyrate as a histone deacetylase inhibitor (HDACi) has led to several clinical trials to assess its effectiveness as a potential cancer treatment. Among various significant roles, butyrate is the main energy source for intestinal epithelial cells, which helps maintain colonic homeostasis. Moreover, people with non-small-cell lung cancer (NSCLC) have distinct gut microbiota from healthy adults and frequently have dysbiosis of the butyrate-producing bacteria in their guts. So, with an emphasis on colon and lung cancer, this review also discusses how the microbiome is crucial in preventing the progression of certain cancers through butyrate production. Further studies should be performed to investigate the underlying mechanisms of how these specific butyrate-producing bacteria can control both colon and lung cancer progression and prognosis.

Potential of Gut Microbial Metabolites in Treating Osteoporosis and Obesity: A Network Pharmacology and Bioinformatics Approach.

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.

Investigating the Anticancer Activity of G-Rh1 Using In Silico and In Vitro Studies (A549 Lung Cancer Cells).

Ginsenoside Rh1 (G-Rh1), a possible bioactive substance isolated from the Korean Panax ginseng Meyer, has a wide range of pharmacological effects. In this study, we have investigated the anticancer efficacy of G-Rh1 via in silico and in vitro methodologies. This study mainly focuses on the two metastatic regulators, Rho-associated protein kinase 1 (ROCK1) and RhoA, along with other standard apoptosis regulators. The ROCK1 protein is a member of the active serine/threonine kinase family that is crucial for many biological processes, including cell division, differentiation, and death, as well as many cellular processes and muscle contraction. The abnormal activation of ROCK1 kinase causes several disorders, whereas numerous studies have also shown that RhoA is expressed highly in various cancers, including colon, lung, ovarian, gastric, and liver malignancies. Hence, inhibiting both ROCK1 and RhoA will be promising in preventing metastasis. Therefore, the molecular level interaction of G-Rh1 with the ROCK1 and RhoA active site residues from the preliminary screening clearly shows its inhibitory potential. Molecular dynamics simulation and principal component analysis give essential insights for comprehending the conformational changes that result from G-Rh1 binding to ROCK1 and RhoA. Further, MTT assay was employed to examine the potential cytotoxicity in vitro against human lung cancer cells (A549) and Raw 264.7 Murine macrophage cells. Thus, G-Rh1 showed significant cytotoxicity against human lung adenocarcinoma (A549) at 100 µg/mL. In addition, we observed an elevated level of reactive oxygen species (ROS) generation, perhaps promoting cancer cell toxicity. Additionally, G-Rh1 suppressed the mRNA expression of RhoA, ROCK1, MMP1, and MMP9 in cancer cell. Accordingly, G-Rh1 upregulated the p53, Bax, Caspase 3, caspase 9 while Bcl2 is downregulated intrinsic pathway. The findings from our study propose that the anticancer activity of G-Rh1 may be related to the induction of apoptosis by the RhoA/ROCK1 signaling pathway. As a result, this study evaluated the functional drug-like compound G-Rh1 from Panax ginseng in preventing and treating lung cancer adenocarcinoma via regulating metastasis and apoptosis.

Binary Effects of Gynostemma Gold Nanoparticles on Obesity and Inflammation via Downregulation of PPARγ/CEPBα and TNF-α Gene Expression.

Nanoscience is a multidisciplinary skill with elucidated nanoscale particles and their advantages in applications to various fields. Owing to their economical synthesis, biocompatible nature, and widespread biomedical and environmental applications, the green synthesis of metal nanoparticles using medicinal plants has become a potential research area in biomedical research and functional food formulations. Gynostemma pentaphyllum (GP) has been extensively used in traditional Chinese medicine to cure several diseases, including diabetes mellitus (DM). This is the first study in which we examined the efficacy of G. pentaphyllum gold nanoparticles (GP-AuNPs) against obesity and related inflammation. GP extract was used as a capping agent to reduce Au2+ to Au0 to form stable gold nanoparticles. The nanoparticles were characterized by using UV-VIS spectroscopy, and TEM images were used to analyze morphology. In contrast, the existence of the functional group was measured using FTIR, and size and shape were examined using XRD analysis. In vitro analysis on GP-AuNPs was nontoxic to RAW 264.7 cells and 3T3-L1 cells up to a specific concentration. It significantly decreased lipid accumulation in 3T3-L1 obese and reduced NO production in Raw 264.7 macrophage cells. The significant adipogenic genes PPARγ and CEPBα and a major pro-inflammatory cytokine TNF-α expression were quantified using RT-PCR. The GP-AuNPs decreased the face of these genes remarkably, revealing the antiadipogenic and anti-inflammatory activity of our synthesized GP-AuNPs. This study represents thorough research on the antiobesity effect of Gynostemma pentaphyllum gold nanoparticles synthesized using a green approach and the efficacy instead of related inflammatory responses.

Characteristics of Panax ginseng Cultivars in Korea and China.

Ginseng (Panax ginseng Meyer) is one of the most important medicinal herbs in Asia. Its pharmacological activity comes from ginsenosides, and its roots are produced commercially for traditional and Oriental medicine. Though 17 Panax species are available around the world, there was a need to develop cultivars adapted to different climatic conditions and resistant to various diseases while still producing high-quality, high-yield roots. Thus, 12 and 9 commercial P. ginseng cultivars have been registered in South Korea and China, respectively. Those varieties show superiority to local landraces. For example, Chunpoong is more highly resistant to rusty rot disease than the local Jakyungjong landrace and has a good root shape; it is highly cultivated to produce red ginseng. The Chinese cultivar Jilin Huangguo Renshen has higher ginsenoside content than its local landraces. This review provides information about P. ginseng cultivars and offers directions for future research, such as intra- and interspecific hybridization.

Diversity of Ginsenoside Profiles Produced by Various Processing Technologies.

Ginseng is a traditional medicinal herb commonly consumed world-wide owing to its unique family of saponins called ginsenosides. The absorption and bioavailability of ginsenosides mainly depend on an individual's gastrointestinal bioconversion abilities. There is a need to improve ginseng processing to predictably increase the pharmacologically active of ginsenosides. Various types of ginseng, such as fresh, white, steamed, acid-processed, and fermented ginsengs, are available. The various ginseng processing methods produce a range ginsenoside compositions with diverse pharmacological properties. This review is intended to summarize the properties of the ginsenosides found in different Panax species as well as the different processing methods. The sugar moiety attached to the C-3, C-6, or C-20 deglycosylated to produce minor ginsenosides, such as Rb1, Rb2, Rc, Rd→Rg3, F2, Rh2; Re, Rf→Rg1, Rg2, F1, Rh1. The malonyl-Rb1, Rb2, Rc, and Rd were demalonylated into ginsenoside Rb1, Rb2, Rc, and Rd by dehydration. Dehydration also produces minor ginsenosides such as Rg3→Rk1, Rg5, Rz1; Rh2→Rk2, Rh3; Rh1→Rh4, Rk3; Rg2→Rg6, F4; Rs3→Rs4, Rs5; Rf→Rg9, Rg10. Acetylation of several ginsenosides may generate acetylated ginsenosides Rg5, Rk1, Rh4, Rk3, Rs4, Rs5, Rs6, and Rs7. Acid processing methods produces Rh1→Rk3, Rh4; Rh2→Rk1, Rg5; Rg3→Rk2, Rh3; Re, Rf, Rg2→F1, Rh1, Rf2, Rf3, Rg6, F4, Rg9. Alkaline produces Rh16, Rh3, Rh1, F4, Rk1, ginsenoslaloside-I, 20(S)-ginsenoside-Rh1-60-acetate, 20(R)-ginsenoside Rh19, zingibroside-R1 through hydrolysis, hydration addition reactions, and dehydration. Moreover, biological processing of ginseng generates the minor ginsenosides of Rg3, F2, Rh2, CK, Rh1, Mc, compound O, compound Y through hydrolysis reactions, and synthetic ginsenosides Rd12 and Ia are produced through glycosylation. This review with respect to the properties of particular ginsenosides could serve to increase the utilization of ginseng in agricultural products, food, dietary supplements, health supplements, and medicines, and may also spur future development of novel highly functional ginseng products through a combination of various processing methods.

Gold Nanoparticles Synthesized with Fresh Panax ginseng Leaf Extract Suppress Adipogenesis by Downregulating PPARγ/CEBPα Signaling in 3T3-L1 Mature Adipocytes.

The obesity rate has been increasing worldwide, which is important because obesity has been linked to the development of various metabolic disorders, such as type 2 diabetes, hypertension, cancer, and stroke. Nanomedicine offers a new approach for treating many diseases, including metabolic disorders such as obesity. In this study, we explored the anti-adipogenic effects of spherical gold nanoparticles synthesized with fresh Panax ginseng leaves (P.g AuNPS) in vitro using 3T3-L1 mature adipocytes. Cell viability was assessed by quantitating preadipocyte growth at different time points. Furthermore, to assess the anti-adipogenic effects of P.g AuNPS, intracellular lipid accumulation was investigated in mature adipocytes. To this end, cells were observed under a microscope and OD measurements were taken after Oil Red O staining. In addition, transcriptional gene regulation was examined by performing real time PCR to assess the levels of adipogenic genes such as PPARγ, CEBPα, CEBPß, Jak2, STAT3, FAS, SREBP-1, and ap2. Moreover, protein levels were evaluated by immunoblotting. Altogether, these results confirm that P.g AuNPS exhibit anti-adipogenic effects at a concentration of 100 µg/ml and that these effects are mediated by the downregulation of PPARγ/CEBPα (major transcription factors) signaling in 3T3-L1 mature adipocytes.

Preparation of Polyethylene Glycol-Ginsenoside Rh1 and Rh2 Conjugates and Their Efficacy against Lung Cancer and Inflammation.

Low solubility and tumor-targeted delivery of ginsenosides to avoid off-target cytotoxicity are challenges for clinical trials. In the present study, we report on a methodology for the synthesis of polyethylene glycol (PEG)-ginsenoside conjugates through a hydrolysable ester bond using the hydrophilic polymer polyethylene glycol with the hydrophobic ginsenosides Rh1 and Rh2 to enhance water solubility and passive targeted delivery. The resulting conjugates were characterized by 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). 1H NMR revealed that the C-6 and C-3 sugar hydroxyl groups of Rh1 and Rh2 were esterified. The conjugates showed spherical shapes that were monitored by field-emission transmission electron microscopy (FE-TEM), and the average sizes of the particles were 62 ± 5.72 nm and 134 ± 8.75 nm for PEG-Rh1and PEG-Rh2, respectively (measured using a particle size analyzer). Owing to the hydrophilic enhancing properties of PEG, PEG-Rh1 and PEG-Rh2 solubility was greatly enhanced compared to Rh1 and Rh2 alone. The release rates of Rh1 and Rh2 were increased in lower pH conditions (pH 5.0), that for pathophysiological sites as well as for intracellular endosomes and lysosomes, compared to normal-cell pH conditions (pH 7.4). In vitro cytotoxicity assays showed that the PEG-Rh1conjugates had greater anticancer activity in a human non-small cell lung cancer cell line (A549) compared to Rh1 alone, whereas PEG-Rh2 showed lower cytotoxicity in lung cancer cells. On the other hand, both PEG-Rh1 and PEG-Rh2 showed non-cytotoxicity in a nondiseased murine macrophage cell line (RAW 264.7) compared to free Rh1 and Rh2, but PEG-Rh2 exhibited increased efficacy against inflammation by greatly inhibiting nitric oxide production. Thus, the overall conclusion of our study is that PEG conjugation promotes the properties of Rh1 for anticancer and Rh2 for inflammation treatments. Depends on the disease models, they could be potential drug candidates for further studies.

Overexpression of Panax ginseng sesquiterpene synthase gene confers tolerance against Pseudomonas syringae pv. tomato in Arabidopsis thaliana.

Sesquiterpenes are an abundant group belonging to the terpenoid family, with a C15 structure comprise of three isoprene units. Many sesquiterpenes are volatile compounds and it act as chemical messenger in plant signalling, particularly in the defense mechanism against biotic and abiotic stresses. Panax ginseng Meyer is important medicinal herbs with various reported pharmacological efficacies in which its triterpenoid saponins, called ginsenosides, were mostly studied. However, there have been few studies on volatile sesquiterpenes compounds regulation on P. ginseng. As slow-growing perennial plant, P. ginseng received many kind of stresses during its cultivation. The pathogen attack is one of the most devastated perturbation for ginseng yield. Thus, we aimed to analyze P. ginseng STS gene (PgSTS) expressions in ginseng organs as well as mono-, sesquiterpenes contents from ginseng seedlings treated with elicitors. qRT-PCR and GC-MS analysis showed that two elicitors- salicylic acid (SA) and methyl jasmonate (MeJA) triggered PgSTS expression at different time points and significantly induced mono-, sesquiterpene yield. Overexpression of PgSTS in Arabidopsis also induced high terpene content and conferred tolerance against Pseudomonas syringae pv. tomato infection. These results suggested that PgSTS transcripts are involved in terpenoid biosynthesis in response to environmental stress mediated by MeJA and SA elicitors; thus, generate tolerance against pathogen attack.

Synthesis and pharmacokinetic characterization of a pH-sensitive polyethylene glycol ginsenoside CK (PEG-CK) conjugate.

The ginsenosides in Panax ginseng have vast structural and pharmacological efficacies. We covalently conjugated polyethylene glycol on the surface of CK (PEG-CK) through an acid-labile ester-linkage that showed increased solubility of CK. HPLC analysis showed that the release of CK was enhanced at acidic pH 5, whereas it was dramatically decreased at physiological pH 7.4. This might enhance the efficacy of CK.

Atopic dermatitis: Pathophysiology, microbiota, and metabolome - A comprehensive review.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. Genetics, environment, and defects in the skin barrier are only a few of the factors that influence how the disease develops. As human microbiota research has advanced, more scientific evidence has shown the critical involvement of the gut and skin bacteria in the pathogenesis of atopic dermatitis. Microbiome dysbiosis, defined by changed diversity and composition, as well as the development of pathobionts, has been identified as a potential cause for recurring episodes of atopic dermatitis. Gut dysbiosis causes "leaky gut syndrome" by disrupting the epithelial lining of the gut, which allows bacteria and other endotoxins to enter the bloodstream and cause inflammation. The same is true for the disruption of cutaneous homeostasis caused by skin dysbiosis, which enables bacteria and other pathogens to reach deeper skin layers or even systemic circulation, resulting in inflammation. Furthermore, it is now recognized that the gut and skin microbiota releases both beneficial and toxic metabolites. Here, this review covers a range of topics related to AD, including its pathophysiology, the microbiota-AD connection, commonly used treatments, and the significance of metabolomics in AD prevention, treatment, and management, recognizing its potential in providing valuable insights into the disease.

Tuft cells - the immunological interface and role in disease regulation.

Tuft cells, also known as taste chemosensory cells, accumulate during parasite colonization or infection and have powerful immunomodulatory effects on substances that could be detrimental, as well as possible anti-inflammatory or antibacterial effects. Tuft cells are the primary source of interleukin (IL)-25. They trigger extra Innate lymphoid type-2 cells (ILC2) in the intestinal lamina propria to create cytokines (type 2); for instance, IL-13, which leads to an increase in IL-25. As tuft cells can produce biological effector molecules, such as IL-25 and eicosanoids involved in allergy (for example, cysteinyl leukotrienes and prostaglandin D2) and the neurotransmitter acetylcholine. Following parasite infection, tuft cells require transient receptor potential cation channel subfamily M member 5 (TRPM5)-dependent chemosensation to produce responses. Secretory tuft cells provide a physical mucus barrier against the external environment and therefore have vital defensive roles against diseases by supporting tissue maintenance and repair. In addition to recent research on tuft cells, more studies are required to understand the distribution, cell turnover, molecular characteristics, responses in various species, involvement in immunological function across tissues, and most importantly, the mechanism involved in the control of various diseases.

A Focused Review on Molecular Signalling Mechanisms of Ginsenosides Anti-Lung Cancer and Anti-inflammatory Activities.

BACKGROUND: Ginseng (Panax ginseng Meyer) is a cultivated medicinal herb that has been widely available in the Asian region since the last century. Ginseng root is used worldwide in Oriental medicine. Currently, the global mortality and infection rates for lung cancer and inflammation are significantly increasing. Therefore, various preventative methods related to the activity of ginsenosides have been used for lung cancer as well as inflammation. METHODS: Web-based searches were performed on Web of Science, Springer, PubMed, and Scopus. A cancer statistical analysis was also conducted to show the current ratio of affected cases and death from lung cancer around the world. RESULTS: Ginsenosides regulate the enzymes that participate in tumor growth and migration, such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), extracellular signalregulated kinases 1/2 (ERK1/2), the gelatinase network metalloproteinase-2 (MMP-2/9) and activator protein 1 (AP-1). In addition, ginsenosides also possess anti-inflammatory effects by inhibiting the formation of proinflammatory cytokines (tumor necrosis factor-α) (TNF-α) and interleukin-1ß (IL-1ß) and controlling the activities of inflammatory signalling pathways, such as NF-κB, Janus kinase2/signal transducer, and activator of transcription 3 (Jak2/Stat3). CONCLUSION: In several in vitro and in vivo models, P. ginseng showed potential beneficial effects in lung cancer and inflammation treatment. In this review, we provide a detailed and up-to-date summary of research evidence for antilung cancer and anti-inflammatory protective effects of ginsenosides and their potential molecular mechanisms.

A review on Impact of dietary interventions, drugs, and traditional herbal supplements on the gut microbiome.

The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.

A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation.

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species and 114 metabolites from the gutMgene database. Further, we used different online-based database platforms to predict 1890 gene targets associated with metabolites. Moreover, DisGeNET, OMIM, and Genecard databases were used to consider 13,104 disease-related gene targets. We used a Venn diagram and various protein-protein interactions (PPIs), KEGG pathways, and GO analyses for the functional analysis of gene targets. Moreover, the subnetwork of protein-protein interactions (through string and cytoscape platforms) was used to select the top 20% of gene targets through degree centrality, betweenness centrality, and closeness centrality. To screen the possible candidate compounds, we performed an analysis of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of metabolites and then found the best binding affinity using molecular docking simulation. (3) Results: Finally, we found the key gene targets that interact with suitable compounds and function against kidney cancer and inflammation, such as MTOR (with glycocholic acid), PIK3CA (with 11-methoxycurvularin, glycocholic acid, and isoquercitrin), IL6 (with isoquercitrin), PTGS2 (with isoquercitrin), and IGF1R (with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, isoquercitrin), showed a lower binding affinity. (4) Conclusions: This study provides evidence to support the positive effects of SCFA-producing microbial metabolites that function against kidney cancer and inflammation and makes integrative research proposals that may be used to guide future studies.

In Vitro Cultivation and Ginsenosides Accumulation in Panax ginseng: A Review.

The use of in vitro tissue culture for herbal medicines has been recognized as a valuable source of botanical secondary metabolites. The tissue culture of ginseng species is used in the production of bioactive compounds such as phenolics, polysaccharides, and especially ginsenosides, which are utilized in the food, cosmetics, and pharmaceutical industries. This review paper focuses on the in vitro culture of Panax ginseng and accumulation of ginsenosides. In vitro culture has been applied to study organogenesis and biomass culture, and is involved in direct organogenesis for rooting and shooting from explants and in indirect morphogenesis for somatic embryogenesis via the callus, which is a mass of disorganized cells. Biomass production was conducted with different types of tissue cultures, such as adventitious roots, cell suspension, and hairy roots, and subsequently on a large scale in a bioreactor. This review provides the cumulative knowledge of biotechnological methods to increase the ginsenoside resources of P. ginseng. In addition, ginsenosides are summarized at enhanced levels of activity and content with elicitor treatment, together with perspectives of new breeding tools which can be developed in P. ginseng in the future.

Discrimination of Dendropanax morbifera via HPLC fingerprinting and SNP analysis and its impact on obesity by modulating adipogenesis- and thermogenesis-related genes.

Dendropanax morbifera (DM), a medicinal plant, is rich in polyphenols and commonly used to treat cancer, inflammation, and thrombosis. However, to date, no study has been conducted on DM regarding the enormous drift of secondary metabolites of plants in different regions of the Republic of Korea and their effects on antiobesity, to explore compounds that play an important role in two major obesity-related pathways. Here, we present an in-depth study on DM samples collected from three regions of the Republic of Korea [Jeju Island (DMJ), Bogildo (DMB), and Jangheung (DMJG)]. We used high-performance liquid chromatography (HPLC) and multivariate component analyses to analyze polyphenol contents (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and rutin), followed by discrimination of the samples in DMJG using single nucleotide polymorphism and chemometric analysis. In silico and in vitro evaluation of major compounds found in the plant extract on two major anti-obesity pathways (adipogenesis and thermogenesis) was carried out. Furthermore, two extraction methods (Soxhlet and ultrasound-assisted extraction) were used to understand which method is better and why. Upon quantifying plant samples in three regions with the polyphenols, DMJG had the highest content of polyphenols. The internal transcribed region (ITS) revealed a specific gel-based band for the authentication of DMJG. PCA and PLS-DA revealed the polyphenol's discriminative power of the region DMJG. The anti-obesity effects of plant extracts from the three regions were related to their polyphenol contents, with DMJG showing the highest effect followed by DMJ and DMB. Ultrasound-assisted extraction yielded a high number of polyphenols compared to that of the Soxhlet method, which was supported by scanning electron microscopy. The present work encourages studies on plants rich in secondary metabolites to efficiently use them for dietary and therapeutic purposes.

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.