Evaluation of the in vitro and in vivo antimicrobial activity of alkaloids prepared from Chelidonium majus L. using MRSA- infected C. elegans as a model host.

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.

Understanding of Diabetes in Tibetan, Mongolian, Miao, Dai, Uygur, and Yi Medicine and Collation of Prevention and Cure Medicines.

Diabetes seriously endangers human health and causes a huge economic burden. With the improvement of people's living standard, the prevalence of diabetes is getting higher and higher, and age is becoming younger. It is an increasingly serious global problem. Therefore, it is imperative to find the drugs to treat diabetes. Ethnic medicine is an important part of the world's medicinal treasure house and has its own unique system. This study systematically combined the theoretical understanding of the prevention and treatment of diabetes of Tibetan, Mongolian, Miao, Dai, Uygur, and Yi people by searching the existing literature studies published until 2021, library collection resources (related ethnic monographs, medical books, standards of medicinal materials, etc.), CNKI, PubMed, and other databases and collected and sorted the relevant medicines. A total of 112 kinds of ethnic medicines for the prevention and treatment of diabetes have been discovered, including plant medicines (105 kinds), animal medicines (6 kinds), and fungal medicines (1 kind). The composition of family and genus, medicinal parts, and life forms of medicinal plants were analyzed, and the number of drugs used in the prevention and treatment of diabetes in each ethnic group was statistically analyzed. The results showed that Rosaceae was at the top of the list, and the drugs used in underground parts accounted for 33.90% of the total, and the medicinal plants were mainly herbaceous, and the Mongolians have the largest number of diabetes medicines. In addition, CNKI, PubMed, and other databases selected "medicinal materials name," "diabetes," and "hypoglycemia" as keywords, the top 30 medicinal materials reported in existing literature were listed, and their Chinese name, the Latin name of the original plant, family and genus, nationality used, medicinal parts, and active ingredients related to the prevention and treatment of diabetes were introduced in detail. Among the 30 medicines, Astragalus membranaceus, Pueraria lobata, and Coptis chinensis are the most commonly used. Through literature research, this study summarized the existing theories of ethnic medicine for the prevention and treatment of diabetes, collected and sorted out ethnic medicine, clarified the potential mechanism of ethnic medicine, and provided effective data compilation. Ethnic medicine has a long history of treating diabetes, and there are abundant medicinal materials, to provide a new idea and basis for treating diabetes.

One-Way Intestinal Perfusion of PVP/VA-Poloxamer 188-Curcuma longa L. Extract Solid Dispersion in Rats In Vivo and Its Effect on HSC-T6 Cell Proliferation.

Turmeric was the dried rhizome of Curcuma longa L., and its extract had important pharmacological effects such as anti-tumor, cholagogic, and antioxidant. However, curcuma extract had poor water solubility and low bioavailability, which had become the main limiting factor for its clinical application. The purpose of this study was to prepare PVP/VA-Poloxamer-188-curcuma extract solid dispersion (PAP-CSD) to improve the solubility and bioavailability of the curcuma extract. The intestinal absorption mechanism of solid dispersion of this extract was studied by one-way intestinal perfusion in rats. PAP-CSD,PVP/VA-curcuma extract solid dispersion (PA-CSD) and Poloxamer-188-curcuma extract solid dispersion (P-CSD) was able to improve the intestinal absorption of the curcuma extract (P < 0.05), and PAP-CSD (combined use of two carriers) was better than that of PA-CSD and P-CSD. CCK8 method was used to investigate the effects of the curcuma extract and PAP-CSD on the proliferation of hepatic stellate cells (HSC)-T6 cells. The inhibitory effect of PAP-CSD on the proliferation of HSC-T6 cells, related to the p38 MAPK pathway, was better than that of the curcuma extract.

The Treatment of Cholecystitis and Cholelithiasis by Tibetan Medicine.

Cholecystitis and cholelithiasis is one of the factors threatening human health. It is very important to find drugs for the treatment of cholecystitis and cholelithiasis. Tibetan medicine is one of the traditional medical systems in China. It has rich experience in treating various diseases. This paper summarizes the treatment of cholecystitis and cholelithiasis through literature review of Tibetan medicine monographs, drug standards, Tibetan medicine, and prescriptions. In the Tibetan medicine system, 170 kinds of Tibetan medicine and 38 kinds of Tibetan prescriptions were found to treat cholecystitis and cholelithiasis. Among them, there are 35 modern researches related to the treatment of cholecystitis and cholelithiasis. Their names, families, medicinal parts, chemical constituents, and pharmacological activities are introduced in detail. These Tibetan medicines and prescriptions may be a precious gift of ancient Tibetan medicine to the world, and may also become potential drug candidates for the treatment of cholecystitis and cholelithiasis. Modern phytochemistry, pharmacology, metabonomics, and/or clinical trials can be used to confirm its medicinal value in the treatment of cholecystitis and cholelithiasis, identify active compounds, clarify its potential mechanism of action, and clarify its toxicity and side effects. This article provides a new idea and source for the treatment of cholecystitis and cholelithiasis.

Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment.

Traditional Chinese medicine (TCM) has good clinical application prospects in diabetes treatment. In addition, TCM is less toxic and/or has fewer side effects and provides various therapeutic effects. Berberine (BBR) is isolated as the main component in many TCM kinds (e.g., Rhizoma Coptidis and Berberidis Cortex). Furthermore, BBR can reduce blood sugar and blood fat, alleviate inflammation, and improve the state of patients. Based on the recent study results of BBR in diabetes treatment, the BBR pharmacokinetics and mechanism on diabetes are mainly studied, and the specific molecular mechanism of related experimental BBR is systematically summarized and analyzed. Clinical studies have proved that BBR has a good therapeutic effect on diabetes, suggesting that BBR may be a promising drug candidate for diabetes. More detailed BBR mechanisms and pathways of BBR need to be studied further in depth, which will help understand the BBR pharmacology in diabetes treatment.

Tibetan Medicines and Tibetan Prescriptions for the Treatment of Diabetes Mellitus.

Diabetes mellitus (DM) is one of the most serious diseases threatening human health and because of that, it is imperative to look for drugs to tackle it. The Tibetan medicine, a traditional medical system used in China, is currently being the focus of research towards the discovery of new effective drugs against several diseases. Based on the literature survey of Tibetan medicine monographs and drug standards, the Tibetan medicine, and Tibetan prescription used in the traditional Tibetan medical system, here, we summarise the methods indicated for DM treatment. In the Tibetan medical system, 56 types of Tibetan medicine and 25 Tibetan prescriptions were found for the treatment of DM. The most commonly used are Curcuma, Berberidis Cortex, and Carthami Flos. Their names, families, medicinal parts, phytochemical components, and pharmacological activities were described in detail in our research. These Tibetan medicines and prescriptions are valuable gifts from the Tibetan medicine to the world and may be the source of potential drugs for the treatment of DM. With the help of modern phytochemistry, pharmacology, metabonomics, and/or clinical trial methods, further research is needed to prove its medicinal value, identify bioactive components, elucidate potential mechanisms of action, and assess potential side effects or toxicity. This study provides the first available data compilation for the ethnic medical knowledge of Tibetan medicine for the treatment of DM, providing new ideas and sources for drugs against DM.

Towards characterizing the regional cerebral perfusion in evaluating the severity of major depression disorder with SPECT/CT.

BACKGROUND: Major depressive disorder (MDD) is a common mental disorder worldwide, but now there is a lack of clinically effective assessment and management of MDD. In this study, we used technetium-99 m ethylcysteinate dimer ([99mTc]ECD) SPECT/CT to characterize the regional cerebral blood flow (rCBF) status of MDD patients, and to explore an objective image assessment model of MDD which is non- or minimally-invasive, convenient and accurate in a clinical setting. METHODS: The severity of MDD was assessed by three trained psychiatrists, based on scores obtained from HAMD and HAMA. [99mTc]ECD rCBF SPECT/CT was performed in 20 healthy controls and 74 unipolar MDD patients before receiving the treatment. The CT attenuation-corrected SPECT images data were automatically registered, analyzed simultaneously by 3D-SSP and eZIS. RESULTS: The mean score of HAMD and HAMA in the MDD patients was 25.49 ± 6.00, and 23.12 ± 5.83, respectively. There was a positive correlation between two scores. The MDD women had higher HAMD scores than MDD men. The decreased rCBF of MDD patients in frontal lobes (bilateral B11, B47 and right B4, B6, B10, B46), temporal lobe (right B21, B41, B42) and cingulated cortex (bilateral B24, B33), while their increased rCBF in occipital lobe (bilateral B17, B19 and left B18). Additionally, the depression severity was negatively correlated with decreased rCBF in left ventral anterior cingulate cortex B24, and was positively correlated with decreased rCBF in left inferior prefrontal gyrus B47 and increased rCBF in right associative visual cortex B19. The anxiety severity was negatively correlated with decreased rCBF in left subgenual cortex B25. CONCLUSIONS: Although the mechanism underlying the correlation is not yet fully understood, our findings indicated that the rCBF SPECT/CT may provide an objective assessment for MDD severity. It might be used monitoring therapeutic efficacy in the management of MDD.

Superparamagnetic iron oxide nanoparticles mediated (131)I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF). METHODS: hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. RESULTS: 131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. CONCLUSIONS: EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.

Sex differences in blood pressure response to antihypertensive therapy in Chinese patients with hypertension.

BACKGROUND: Sex-specific responses to antihypertensive drugs are not very well understood. OBJECTIVE: To investigate sex-related differences in blood pressure response to antihypertensive drugs in a community-based prospective clinical trial. METHODS: We recruited 3535 untreated hypertensive patients (2326 women), aged 40-75 years, from 7 rural communities in China. Subjects were randomized to 1 of 4 drug groups: atenolol, hydrochlorothiazide (HCTZ), captopril, or sustained-released nifedipine; duration of the study was 8 weeks. Mean blood pressure reduction, blood pressure control rates, and frequency of adverse events were compared between men and women. RESULTS: Women had a better response to HCTZ in relation to diastolic blood pressure (1.8 mm Hg lower) than did men (p < 0.05) and were 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). In the atenolol group, mean systolic blood pressure decreased 3.9 mm Hg more in women than in men (p < 0.05), and women were 65% more likely to reach the control goal of systolic blood pressure and 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). Significant sex-related differences were also found in drug-related adverse events in the nifedipine group (15.8% in women vs 9.8% in men; p = 0.017) and in the captopril group (14.3% in women vs 8.4% in men; p = 0.005), but no differences were seen with HCTZ or atenolol. CONCLUSIONS: Women have better blood pressure responses to HCTZ and atenolol and experience more adverse effects with sustained-release nifedipine and captopril than do men, indicating that sex should be taken into account when selecting antihypertensive drugs.