Network pharmacology and bioinformatics analysis identified essential genes of Jingulian in the treatment of rheumatoid arthritis and COVID-19.

Background: Patients with rheumatoid arthritis (RA) may be more susceptible to infection by coronavirus disease-19 (COVID-19) due to immune system dysfunction. However, there are still insufficient treatment strategies for patients with RA and COVID-19. Since Jingulian is a traditional Chinese medicine (TCM) with anti-viral and immune regulatory functions, our study aims to explore the detailed mechanisms of Jingulian in treating patients with RA and COVID-19. Methods: All the components of Jingulian were retrieved from pharmacology databases. Then, a series of network pharmacology-based analyses and molecular docking were used to understand the molecular functions, core targets, related pathways, and potential therapeutic targets of Jingulian in patients with RA/COVID-19. Results: A total of 93 genes were identified according to the disease-compound-target network. We investigated that the main targets, signaling pathways, and biological functions of Jingulian in RA and COVID-19. Our results indicated that Jingulian may treat patients with RA/COVID-19 through immune processes and viral processes. Moreover, the results of molecular docking revealed that tormentic acid was one of the top compounds of Jingulian, which had high affinity with Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR) in patients with RA/COVID-19. Furthermore, 5 core targets of Jingulian were also identified, including JAK1, Janus kinase 2 (JAK2), STAT3, lymphocyte specific protein tyrosine kinase (LCK), and EGFR. Conclusions: Tormentic acid in Jingulian may regulate JAK1, STAT3, and EGFR, and might play a critical role in RA/COVID-19.

Quantitative probabilistic assessment of caffeine intake from tea in Chinese adult consumers based on nationwide caffeine content determination and tea consumption survey.

Caffeine has known effects on the central nervous and cardiovascular systems. An intake up to 400 mg/day does not give rise to health concerns. Tea, a major source of caffeine, is highly consumed in China. However, the potential health risk of caffeine from tea has not been well evaluated. The present study assessed caffeine intake levels from tea for Chinese adult consumers. We collected 1,398 samples of green, black, dark, jasmine, oolong, white, and yellow tea from 17 provinces. The caffeine content was determined by HPLC. The average contents were 27 (oolong tea) - 43 (yellow tea) mg/g. The leaching rate of caffeine into the water was about 100%. Tea consumption data were from the National Beverage Consumption Survey 2013-2014. Monte Carlo simulations were applied to estimate the distribution of caffeine intake. The average caffeine intake from tea was 180 mg/day of all consumers. Green, dark, and black tea were the primary sources. Males (197 mg/day) consumed more caffeine than females (136 mg/day) on average, but females older than 71 years had the highest intake level (259 mg/day) among all subgroups. Over 90% of Chinese adult tea drinkers have caffeine intake under 400 mg/day.

Role of lipoic acid in multiple sclerosis.

Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with multiple sclerosis (MS). This systematic review aimed to provide a comprehensive overview of both in vitro and in vivo studies describing the pharmacokinetics, efficacy, safety, and mechanism of LA in MS-related experiments and clinical trials. A total of 516 records were identified by searching five databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane Library. Overall, we included 20 studies reporting LA effects in cell and mouse models of MS and 12 studies reporting LA effects in patients with MS. Briefly, cell experiments revealed that LA protected neurons by inhibiting the expression of inflammatory mediators and activities of immune cells. Experimental autoimmune encephalomyelitis mouse experiments demonstrated that LA consistently reduced the number of infiltrating immune cells in the central nervous system and decreased the clinical disability scores. Patients with MS showed relatively stable Expanded Disability Status Scale scores and better walking performance with few adverse events after the oral administration of LA. Notably, heterogeneity of this evidence existed among modeling methods, LA usage, MS stage, and trial duration. In conclusion, this review provides evidence for the anti-inflammatory and antioxidative effects of LA in both in vitro and in vivo experiments; therefore, patients with MS may benefit from LA administration. Whether LA can be a routine supplementary therapy warrants further study.

Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports.

Primary carnitine deficiency (PCD) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. When carnitine cannot be transported into the cells, fatty acid oxidation is impaired, resulting a variety of symptoms, such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The clinical manifestations and outcomes of different cases with PCD vary among patients. The present case report focused on two sisters with PCD. The younger sister presented with intractable epilepsy, and the older sister presented with reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harbored homozygous mutations, whereas their parents presented heterozygous mutations. Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine. The metabolic cardiomyopathy of the older sister improved following 3 months of treatment. However, the epilepsy of the younger sister was recurrent with oral antiepileptic therapy lasting one year and eight months, and epilepsy was finally controlled following right cerebral resection. The present case report demonstrated that the clinical manifestations presented by patients with PCD within the same family were different. The results indicated that treatment with levocarnitine supplementation should be initiated as soon as possible before irreversible organ damage occurs. In addition, metabolic decompensation and cardiac muscle functions were improved following carnitine supplementation. The resection of the severely diseased unilateral brain combined with carnitine supplementation and antiepileptic therapy may be an effective treatment for PCD with intractable epilepsy complications.

D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway.

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.

A new analog of pyrrolezanthine from the roots of Reynoutria ciliinervis (Nakai) Moldenke.

In the present study, a new analogue of pyrrolezanthine (1) was isolated from the roots of Reynoutria ciliinervis (Nakai) Moldenke. Its structure was elucidated mainly by NMR, HR-ESI-MS and the single-crystal X-ray diffraction spectroscopic data. Meanwhile, the antimicrobial activity of compound 1 was measured, it exhibited potent antifungal activity against Sclerotinia sclerotiorum with MIC value of 31.2 µg/mL.

Determination of theanine and gamma-aminobutyric acid in tea by high performance- liquid chromatography with precolumn derivatization.

A method of precolumn derivatization-high performance liquid chromatography (HPLC) for the determination of theanine and gamma-aminobutyric acid (GABA) in tea was established. o-Phthalaldehyde (OPA) and N-acetyl-L-cysteine (NAC) were chosen as the derivatization reagents. The effects of teapolyphenol (Tp), proline (Pro) and Vitamin C (Vc) on derivatization yields were investigated. The results indicated that Vc not only stabilized the stock solution of OPA, but also enhanced the yield of GABA derivative. However, the yield of theanine derivative was less affected. The HPLC separation system was also optimized. The resolution of the derivatives was improved by adjusting the pH value and phosphate-citric buffer concentration of the mobile phase. The limits of detection (LODs) for GABA and theanine were 3.01 x 10(-5) mmol/L and 7.98 x 10(-5) mmol/L, and the limits of quantification (LOQs) were 9.99 x 10(-5) mmol/L and 2.658 x 10(-4) mmol/L, respectively. The linear ranges of GABA and theanine were 0.01 - 0.4 mmol/L with the correlation coefficient of 0.996 and 0.05 - 0.8 mmol/L with the correlation coefficient of 0.995, respectively. The main recoveries for GABA and theanine in green tea, Oolong tea, and black tea, ranged from 99.29% to 119.60% and from 62.88% to 141.06% respectively. The method with simple procedure and efficient separation was proved to be suitable for the determination of GABA and theanine in tea.