Herbs’ Disease-matched Pharmacological Mechanisms of HuanglianJiedu Decoction in Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease

Along with cognitive deficit, behavioral and psychological symptoms in dementia (BPSD) is another characteration of Alzheimer's disease that hamper clinical management and exacerbate burden for caregivers. However, therapeutic management of BPSD remains challenging. HuanglianJiedu decoction (HLJDD), a traditional Chinese prescription which contains Coptidis rhizome(Huang lian), Scutellariae radix (Huang-qin), Phellodendri chinrnsis cortex (Huang-bai) and Gardeniae fructus (Zhi-zi), is applied to treat BPSD. So elucidating the herbs’ disease-matched pharmacological mechanisms underlying HLJDD, further put forward each herbs’ disease-matched combination are critical to the application of HLJDD. In this study, network pharmacology was used to determine the targets and biological processes regulated by HLJDD in the treatment of BPSD. Moreover, molecular docking was utilized to evaluate the binding activity between the herbs' main active ingredients and neurotransmitter receptors. The results showed that the KEGG signaling pathway of HLJDD in treating BPSD mainly lies in TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Scutellariae radix and Phellodendri chinrnsis cortex exhibited better anti-BPSD effects when compared to Coptidis rhizoma and Gardeniae fructus. Scutellariae radix exhibited superior anti-neuroinflammation functions, with better blood vessel regulation effects. Phellodendri chinrnsis cortex showed a higher binding affinity to the dopamine D2 receptor (DRD2) and 5-hydroxytryptamine receptor 2A (HTR2A). Coptidis rhizoma and Gardeniae fructus were better in neuronal signaling. In conclusion, for treating BPSD, Scutellariae radix and Phellodendri chinrnsis cortex are the principal herbs while Coptidis rhizoma and Gardeniae fructus are the ancillary herbs. Beta-sitosterol, stigmasterol, chelerythrine, campesterol and berberine are the potential effective ingredients in treating BPSD.

Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPARγ/RXR Signaling in Reflux Esophagitis

Objective. Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). Methods. After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). Results. SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. Conclusion. Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.

The Bioactivity of Scutellariae Radix Carbonisata-Derived Carbon Dots: Antiallergic Effect

Chinese medicine is a treasure of the Chinese nation, and charcoal drugs are a class of medicine with distinctive characteristics. Scutellariae Radix Carbonisata (SRC) could be a sort of calcined herb medicate that has been utilized in traditional Chinese medicine (TCM) clinics to treat hypersensitivities. However, to date, the function of the carbonized part and action mechanisms of SRCs have not been elucidated. In this study, novel water-soluble carbon dots (CDs, named SRC-CDs) ranging from 2 to 9 nm were observed and separated from aqueous extracts of SRC. These SRC-CDs were characterized using transmission electron microscopy (TEM) and high-resolution TEM, as well as Fourier transform infrared, ultraviolet-visible, and fluorescence spectroscopy, to determine particle size, morphology, chemical structure, and optical properties. Then, the in vitro antiallergic efficacy of the SRC-CDs was studied in a C48/80-induced RBL-2H3 cell model, in which remarkable antiallergic effects were revealed. These results will provide new solution directions and technical methods for follow-up research of charcoal drugs and new understanding of potential biomedical applications of CDs.

Which East Asian herbal medicines can decrease viral infections?

Whilst Western research for the COVID-19 crisis focuses on vaccination, in East Asia traditional herbal prescriptions are studied for SARS-CoV2 therapy. In Japan, Maoto (Ephedrae herba 4 g, Armeniacae semen 4 g, Cinnamomi cortex 3 g, and Glycyrrhizae radix 2 g, JPXVII) is used based on clinical evidence for its effect on early phase influenza (also caused by RNA viruses) comparable to that of oseltamivir. The Health Ministry of Thailand has approved Andrographis paniculata (Jap. Senshinren) extracts for treatment of COVID-19. Its combination (4 g) with Maoto, Maoto-ka-senshinren, seems most promising for the treatment of viral pandemics. In China, the official guideline for COVID-19 treatment contains TCM medications with antiviral, as well as immunmodulatory and anti-inflammatory effects such as: Qing-Fei-Pai-Du-Tang (Jap. Seihai-haidokuto) contains 21 drugs; Shufeng Jiedu Jiaonang (Bupleuri radix 8 g, Forsythiae fructus 8 g, Glycyrrhizae radix 4 g, Isatidis radix 8 g, Patriniae herba 8 g, Phragmitis rhizoma 6 g, Polygoni cuspidati rhizoma 10 g, Verbenae herba 8 g); Fufang Yuxingcao Heiji (Forsythiae fructus 0.6 g, Houttuyniae herba 6 g, Isatidis radix 1.5 g, Lonicerae flos 0.6 g, Scutellariae radix 1.5 g) first gained prominence during the 2002 SARS epidemic. With no Western medicine available, the following overview discusses efficacy and mechanisms in view of viral entry and replication of different East Asian herbal remedies for COVID-19 treatment.

Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

This study aims to analyze the targets of the effective active ingredients of Scutellariae radix-Coptidis rhizoma drug pair (SCDP) in ulcerative colitis (UC) by network pharmacology and molecular docking and to explore the associated therapeutic mechanism. The effective active ingredients and targets of SCDP were determined from the TCMSP database, and the drug ingredient-target network was constructed using the Cytoscape software. The disease targets related to UC were searched in GeneCards, DisGeNET, OMIM, and DrugBank databases. Then, the drug ingredient and disease targets were intersected to construct a protein-protein interaction network through the STRING database. The Metascape database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the predicted targets of SCDP for UC. The Autodock software was used for molecular docking between the main active ingredient and the core target to evaluate the binding ability. SCDP has 43 effective active ingredients and 134 intersection targets. Core targets included AKT1, TP53, IL-6, VEGFA, CASP3, JUN, TNF, MYC, EGFR, and PTGS2. GO functional enrichment analysis showed that biological process was mainly associated with a cytokine-mediated signaling pathway, response to an inorganic substance, response to a toxic substance, response to lipopolysaccharide, reactive oxygen species metabolic process, positive regulation of cell death, apoptotic signaling pathway, and response to wounding. KEGG enrichment analysis showed main pathway concentrations were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, bladder cancer, IL-17 signaling pathway, apoptosis, p53 signaling pathway, and PI3K-Akt signaling pathway. The drug active ingredient-core target-key pathway network contains 41 nodes and 108 edges, of which quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol are important active ingredients; PTGS2, CASP3, TP53, IL-6, TNF, and AKT1 are important targets; and the pathways involved in UC treatment include pathways in cancer, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic, apoptosis, IL-17 signaling pathway and herpes simplex infection. The active ingredient has a good binding capacity to the core target. SCDP key active ingredients are mainly quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol, which function mainly by regulating targets, such as PTGS2, CASP3, TP53, IL-6, TNF, and AKT1, and are associated with multiple signaling pathways as pathways in cancer, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathways.

Constituents, Pharmacokinetics, and Pharmacology of Gegen-Qinlian Decoction

Gegen-Qinlian decoction (GQD) is a classic traditional Chinese medicine (TCM) formula. It is composed of four TCMs, including Puerariae Lobatae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. GQD is traditionally and clinically used to treat both the “external and internal symptoms” of diarrhea with fever. In this review, key words related to GQD were searched in the Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and other databases. Literature published mainly from 2000 to 2020 was screened and summarized. The main constituents of GQD could be classified into eight groups according to their structures: flavonoid C-glycosides, flavonoid O-glucuronides, benzylisoquinoline alkaloids, free flavonoids, flavonoid O-glycosides, coumarins, triterpenoid saponins, and others. The parent constituents of GQD that enter circulation mainly include puerarin and daidzein from Puerariae Lobatae Radix, baicalin and wogonoside from Scutellariae Radix, berberine and magnoflorine from Coptidis Rhizoma, as well as glycyrrhetinic acid and glycyrrhizic acid from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. GQD is effective against inflammatory intestinal diseases, including diarrhea, ulcerative colitis, and intestinal adverse reactions caused by chemotherapeutic agents. Moreover, GQD has significant effects on metabolic diseases, such as nonalcoholic fatty liver and type 2 diabetes. Furthermore, GQD can be used to treat lung injury. In brief, the main constituents, the pharmacokinetic and pharmacological profiles of GQD were summarized in this review. In addition, several issues of GQD including effective constituents, interactions between the constituents, pharmacokinetics, interaction potential with drugs and pharmacological effects were discussed, and related future researches were prospected in this review.

Neuraminidase 1 and its Inhibitors from Chinese Herbal Medicines: An Emerging Role for Cardiovascular Diseases

Neuraminidase, also known as sialidase, is ubiquitous in animals and microorganisms. It is predominantly distributed in the cell membrane, cytoplasmic vesicles, and lysosomes. Neuraminidase generally recognizes the sialic acid glycosidic bonds at the ends of glycoproteins or glycolipids and enzymatically removes sialic acid. There are four types of neuraminidases, named as Neu1, Neu2, Neu3, and Neu4. Among them, Neu1 is the most abundant in mammals. Recent studies have revealed the involvement of Neu1 in several diseases, including cardiovascular diseases, diabetes, cancers, and neurological disorders. In this review, we center the attention to the role of Neu1 in cardiovascular diseases, including atherosclerosis, ischemic myocardial injury, cerebrovascular disease, congenital heart disease, and pulmonary embolism. We also summarize inhibitors from Chinese herbal medicines (CHMs) in inhibiting virus neuraminidase or human Neu1. Many Chinese herbs and Chinese herb preparations, such as Lonicerae Japonicae Flos, Scutellariae Radix, Yupingfeng San, and Huanglian Jiedu Decoction, have neuraminidase inhibitory activity. We hope to highlight the emerging role of Neu1 in humans and potentially titillate interest for further studies in this area.

Novel Combination of HuanglianJiedu Decoction in Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease

Alzheimer's disease (AD) is characterized by progressive cognitive decline. Besides cognitive deficit, AD is also characterized by behavioral and psychological symptoms in dementia (BPSD). However, therapeutic management of BPSD remains challenging. HuanglianJiedu decoction (HLJDD), a traditional Chinese prescription, consisting of four herbs, is applied to treat AD, especially AD with BPSD. Though HLJDD, has the traditional combination with the principal herb Coptidis rhizoma (Huang-lian), it might, however, not be suitable for treating BPSD. Elucidating the mechanism underlying each herb is critical to the disease-matched combination of HLJDD. In this study, network pharmacology was used to determine the targets and biological processes regulated by HLJDD in the treatment of BPSD. Moreover, molecular docking was utilized to evaluate the binding activity between the herbs' main active ingredients and neurotransmitter receptors. The results showed that Scutellariae radix (Huang-qin) and Phellodendri chinrnsis cortex (Huang-bai) exhibited better anti-BPSD effects when compared to Coptidis rhizoma and Gardeniae fructus (Zhi-zi). Scutellariae radix exhibited superior anti-neuroinflammation functions, with better blood vessel regulation effects. Phellodendri chinrnsis cortex showed a higher binding affinity to the dopamine D2 receptor (DRD2) and 5-hydroxytryptamine receptor 2A (HTR2A). Coptidis rhizoma and Gardeniae fructus were better in neuronal signaling. In conclusion, for treating BPSD, Scutellariae radix and Phellodendri chinrnsis cortex are the principal herbs while Coptidis rhizoma and Gardeniae fructus are the ancillary herbs.

The comprehensive quality evaluation of scutellariae radix based on HPLC fingerprint and antibacterial activity

Scutellaria Radix, a traditional Chinese medicine, studies on its main active ingredient are limited. In this study, the purpose was to investigate the quality difference of Scutellariae Radix from different origins based on chemical components and biological activities. The chromatographic fingerprints of Scutellariae Radix from 33 origins were established using HPLC, and the antibacterial activities were studied with the microdilution method. Moreover, orthogonal partial least-square regression, pearson correlational analysis and grey relational analysis methods were performed to explore the relationship between the compositions and bioactivities. In addition, and origin identification model was established to comprehensively evaluate the quality of Scutellariae Radix. The results showed that Scutellariae Radix had in-vitro antibacterial effect on Staphylococcus aureus, and the best were in Gansu, Shandong Province. Multivariate statistical analysis common showed that three components were positively correlated with antibacterial activity, which were respectively wogonin, baicalein and oroxylin. In conclusion, the quality of Scutellariae Radix varies greatly from different origins, and the better was in Gansu and Shandong Province. This work successfully provides a general model that combined the chromatographic fingerprint and bioactivity assay to study the spectrum–effect relationships, which could be used to discover the primary active ingredients in traditional Chinese medicines.