The interaction of anti-inflammatory and anti-tumor components in the traditional Chinese medicine Solanum lyratum Thunb.

Solanum lyratum Thunb is a traditional Chinese medicinal with a significant clinical outcome for tumor treatment; however, chemicals or fractions separated from the herb did not exhibit strong and comparable efficacy. To investigate the potential synergy or antagonism among chemicals in the extract, we obtained the compounds solavetivone (SO), tigogenin (TI) and friedelin (FR) from the herb. The anti-tumor effects of these three monomer compounds alone or in combination with the anti-inflammatory compound DRG were also tested in this study. SO, FR and TI used alone did not inhibit the proliferation of A549 and HepG2 cells, but the combination of the three achieved 40% inhibition. In vitro anti-inflammatory analysis showed that DRG had a stronger anti-inflammatory effect than TS at the same concentration, and the combination of DRG with SO, FR or TI inhibited the anti-tumor effect of DRG. This is the first study that documented the synergistic and antagonistic interactions between different compounds in a single herb.

The Deterioration of Agronomical Traits of the Continuous Cropping of Stevia Is Associated With the Dynamics of Soil Bacterial Community.

Stevia rebaudiana Bertoni is grown worldwide as an important, natural sweetener resource plant. The yield of steviol glycosides (SVglys) is greatly influenced by continuous cropping. In this study, we collected the roots, rhizosphere soils, and bulk soils from 2 years of continuous cropping (Y2) and 8 years of continuous cropping (Y8). A high-throughput sequencing technology based on Illumina Hiseq 2500 platform was used to study the structure and diversity of bacterial communities in the roots and soils of stevia with different years of continuous cropping. The results demonstrated that although the content of a group of SVglys was significantly increased in stevia of long-term continuous cropping, it inhibited the growth of plants and lowered the leaf dry weight; as a result, the total amount of SVglys was significantly decreased. Meanwhile, continuous cropping changed the physicochemical properties and the bacterial composition communities of soil. The different sampling sources of the root, rhizosphere soil, and bulk soil had no impact on the richness of bacterial communities, while it exhibited obvious effects on the diversity of bacterial communities. Continuous cropping had a stronger effect on the bacterial community composition in rhizosphere soil than in root and bulk soil. Based on linear discriminant analysis effect size (LEfSe), in the rhizosphere soil of Y8, the relative abundance of some beneficial bacterial genera of Sphingomonas, Devosia, Streptomyces, and Flavobacterium decreased significantly, while the relative abundance of Polycyclovorans, Haliangium, and Nitrospira greatly increased. Moreover, the soil pH and nutrient content, especially the soil organic matter, were correlated with the relative abundance of predominant bacteria at the genus level. This study provides a theoretical basis for uncovering the mechanism of obstacles in continuous stevia cropping and provides guidance for the sustainable development of stevia.

Addition of Vegetable Oil to Improve Triterpenoids Production in Liquid Fermentation of Medicinal Fungus Antrodia cinnamomea.

The liquid fermentation of Antrodia cinnamomea is a promising alternative source for fungus production compared to the wildly grown fruiting body. Elicitation is a strong tool to enhance the productivity in microbial cells to obtain more compounds of interest. In this study, in order to improve the fungus growth and its terpenoids production, various vegetable oils were added in the fermentation broth of A. cinnamomea. It was found that corn oil from a group of vegetable oils exhibited the best effect on the biomass and triterpenoid content. After optimization, the initial addition of 1% (v/v) corn oil plus the inoculation of 10% (v/v) mycelia led to a maximum triterpenoid yield (532.3 mg L-1), which was increased as much as fourfold compared to the blank control. Differential transcriptome analysis demonstrated that corn oil significantly enriched several metabolic pathways including glycolysis/gluconeogenesis, propanoate metabolism and transmembrane hydrophobins. The enriched pathways interacted with deferentially expressed genes (DEGs) induced by corn oil treatment. Our research provides a potential strategy for the large production of triterpenoids by the improved fermentation of A. cinnamomea.

Lifestyle and Comorbidity-Related Risk Factors of Severe and Critical COVID-19 Infection: A Comparative Study Among Survived COVID-19 Patients in Bangladesh.

BACKGROUND: Severe COVID-19 infections have already taken more than 4 million lives worldwide. Factors, such as socio-demographics, comorbidities, lifestyles, environment, and so on, have been widely discussed to be associated with increased severity in many countries. The study aimed to determine the risk factors of severe-critical COVID-19 in Bangladesh. METHODS: This was a comparative cross-sectional study among various types of COVID-19 patients (both hospitalized and non-hospitalized) confirmed by reverse transcription polymerase chain reaction (RT-PCR). We have selected 1500 COVID-19 positive patients using a convenient sampling technique and analyzed lifestyle and comorbidity-related data using IBM SPSS-23 statistical package software. Chi-square test and multinomial logistic regression were used to determine risk factors of life-threatening COVID-19 infection. RESULTS: The mean age of the study participants was 43.23 (±15.48) years. The study identified several lifestyle-related factors and common commodities as risk factors for severe-critical COVID-19. The patient's age was one of the most important predictors, as people >59 years were at higher risk (AOR=18.223). Among other lifestyle factors, active smoking (AOR=1.482), exposure to secondary smoking (AOR=1.728), sleep disturbance (AOR=2.208) and attachment with SLT/alcohol/substance abuse (AOR=1.804) were identified as significant predictors for severe-critical COVID-19. Patients those were overweight/obese (AOR=2.105), diabetic (AOR=4.286), hypertensive (AOR=3.363), CKD patients (AOR=8.317), asthma patients (AOR=2.152), CVD patients (AOR=7.747) were also at higher risk of severe-critical COVID-19 infection. CONCLUSION: This study has identified several vital lifestyles and comorbidity-related risk factors of severe-critical COVID-19. People who have these comorbidities should be under high protection, and risky lifestyles of the general population should modify through the proper educational campaign.

Metabolomic and Pharmacologic Insights of Aerial and Underground Parts of Glycyrrhiza uralensis Fisch. ex DC. for Maximum Utilization of Medicinal Resources.

The roots of Glycyrrhiza spp. have been utilized in Traditional Chinese medicine (TCM) for thousands of years. Non-traditional (aerial) parts constitute a large portion of the biomass of Glycyrrhiza plants and are mostly discarded after harvesting the roots and rhizomes. Through comparative phytochemical and anti-inflammatory activity analyses, this study explored the potential benefits of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. as medicinal materials. First, a combined approach based on GC/MS and UHPLC-ESI-QTof MS analysis was adopted for the identification and quantitative examination of medicinally important compounds from G. uralensis. Additionally, a bioassay-guided fractioning of ethanolic extracts of G. uralensis leaf material was performed and its anti-inflammatory activity was tested. The aerial portion of G. uralensis was rich in medicinally important compounds. Two compounds (henicosane-1 and decahydroisoquinoline-2) were found to exert a significant anti-inflammatory effect, inhibiting the release of pro-inflammatory mediators (NO and PGE2) and cytokines (IL-1ß, IL6, and TNF-α), without exerting cytotoxic effects. Moreover, both compounds down-regulated iNOS and COX-2 mRNA expression. These results suggest that non-traditional parts of G. uralensis are suitable sources of bioactive metabolites that can be explored for medicinal purposes.

Genome Sequence of a SARS-CoV-2 Strain from a COVID-19 Clinical Sample from the Khagrachari District of Bangladesh.

This study describes the genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain detected in the nasopharyngeal swab sample of a coronavirus disease 2019 (COVID-19) patient from the southeastern Khagrachari District of Bangladesh.

Evaluation of Various Solvent Extracts of Tetrastigma leucostaphylum (Dennst.) Alston Leaves, a Bangladeshi Traditional Medicine Used for the Treatment of Diarrhea.

Tetrastigma leucostaphylum (TL) is an important ethnic medicine of Bangladesh used to treat diarrhea and dysentery. Hence, current study has been designed to characterize the antidiarrheal (in vivo) and cytotoxic (in vitro) effects of T. leucostaphylum. A crude extract was prepared with methanol (MTL) and further partitioned into n-hexane (NTL), dichloromethane (DTL), and n-butanol (BTL) fractions. Antidiarrheal activity was investigated using castor oil induced diarrhea, enteropooling, and gastrointestinal transit models, while cytotoxicity was evaluated using the brine shrimp lethality bioassay. In antidiarrheal experiments, all doses (100, 200, and 400 mg/kg) of the DTL extract significantly reduced diarrheal stool frequency, volume and weight of intestinal contents, and gastrointestinal motility in mice. Similarly, in the cytotoxicity assay, all extracts exhibited activity, with the DTL extract the most potent (LC50 67.23 µg/mL). GC-MS analysis of the DTL extract identified 10 compounds, which showed good binding affinity toward M3 muscarinic acetylcholine, 5-HT3, Gut inhibitory phosphodiesterase, DNA polymerase III subunit alpha, and UDP-N-acetylglucosamine-1 carboxyvinyltransferase enzyme targets upon molecular docking analysis. Although ADME/T analyses predicted the drug-likeness and likely safety upon consumption of these bioactive compounds, significant toxicity concerns are evident due to the presence of the known phytotoxin, 2,4-di-tert-butylphenol. In summary, T. leucostaphylum showed promising activity, helping to rationalize the ethnomedicinal use and importance of this plant, its safety profile following both acute and chronic exposure warrants further investigation.

Annotation of genes involved in high level of dihydromyricetin production in vine tea (Ampelopsis grossedentata) by transcriptome analysis.

BACKGROUND: Leaves of the medicinal plant Ampelopsis grossedentata, which is commonly known as vine tea, are used widely in the traditional Chinese beverage in southwest China. The leaves contain a large amount of dihydromyricetin, a compound with various biological activities. However, the transcript profiles involved in its biosynthetic pathway in this plant are unknown. RESULTS: We conducted a transcriptome analysis of both young and old leaves of the vine tea plant using Illumina sequencing. Of the transcriptome datasets, a total of 52.47 million and 47.25 million clean reads were obtained from young and old leaves, respectively. Among 471,658 transcripts and 177,422 genes generated, 7768 differentially expressed genes were identified in leaves at these two stages of development. The phenylpropanoid biosynthetic pathway of vine tea was investigated according to the transcriptome profiling analysis. Most of the genes encoding phenylpropanoid biosynthesis enzymes were identified and found to be differentially expressed in different tissues and leaf stages of vine tea and also greatly contributed to the biosynthesis of dihydromyricetin in vine tea. CONCLUSIONS: To the best of our knowledge, this is the first formal study to explore the transcriptome of A. grossedentata. The study provides an insight into the expression patterns and differential distribution of genes related to dihydromyricetin biosynthesis in vine tea. The information may pave the way to metabolically engineering plants with higher flavonoid content.

Hepatitis C virus treatment in people who inject drugs (PWID) in Bangladesh.

BACKGROUND: Given the considerable social marginalization experienced by people who inject drugs (PWID), treatment of hepatitis C virus (HCV) in this population presents unique challenges. This study assessed the feasibility of treating HCV infection with direct-acting antiviral (DAA) medications among PWID receiving harm reduction services from a Drop-in-Center in Dhaka, Bangladesh. METHODS: In this prospective study conducted between December 2016 and May 2018, 200 PWID with either recent injecting drug use (i.e., within the previous two months) or a history of injecting drug use and are currently receiving opioid substitution therapy were recruited. Blood was collected to conduct relevant laboratory tests. Eligible PWID who tested positive for HCV RNA (n = 55), were provided daily daclatasvir (60 mg) and sofosbuvir (400 mg) for 12 weeks after which adherence level, sustained virologic response (SVR), and reinfection were assessed. RESULTS: At baseline, 40% (n = 79) of the 200 participants recruited to the study tested positive for antibodies to HCV and 34% (n = 68) had detectable HCV RNA in their blood. Of 55 eligible PWID who initiated treatment, 93% (n = 51) completed treatment while 87% (n = 48) were available for follow-up SVR assessment, all of whom achieved SVR. Thus, intent-to-treat SVR was 87% and the modified intent-to-treat SVR was 100% with one reinfection (4•2 cases per 100 person-years). Further, 75% (i.e., 41 out of the 55 participants) were at least 90% adherent to therapy. CONCLUSION: Our findings strongly suggest that HCV treatment using sofosbuvir+daclatasvir for PWID enrolled in existing harm reduction programs in Bangladesh is feasible but may require additional interventions such as Opioid Substitution Therapy, intense follow up by outreach workers, and services and counselling provided by full time clinicians.

Investigation of the Biological Activities and Characterization of Bioactive Constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & Mondal Leaves through In Vivo, In Vitro, and In Silico Approaches.

Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P < 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines.

Qualitative and quantitative ethnobotanical study of the Pangkhua community in Bilaichari Upazilla, Rangamati District, Bangladesh.

BACKGROUND: The present study documents the ethnomedicinal knowledge among the traditional healers of the Pangkhua indigenous community of Bangladesh. The documented data from this area was quantitatively analyzed for the first time. We aimed to record ethnomedicinal information from both the traditional healers and also the elderly men and women of the community, in order to compile and document all available information concerning plant use and preserve it for the coming generations. We aimed to compare how already known species are used compared to elsewhere and particularly to highlight new ethnomedicinal plant species alongside their therapeutic use(s). METHODS: All ethnomedicinal information was collected following established techniques. Open-ended and semi-structured techniques were primarily utilized. Data was analyzed using different quantitative indices. The level of homogeneity between information provided by different informants was calculated using the Informant Consensus Factor. All recorded plant species are presented in tabular format, alongside corresponding ethnomedicinal usage information. RESULTS: This investigation revealed the traditional use of 117 plant species, distributed among 104 genera and belonging to 54 families. There was strong agreement among the informants regarding ethnomedicinal uses of plants, with Factor of Informant Consensus (FIC) values ranging from 0.50 to 0.66, with the highest number of species (49) being used for the treatment of digestive system disorders (FIC 0.66). In contrast, the least agreement (FIC = 0.50) between informants regarding therapeutic uses was observed for plants used to treat urinary disorders. The present study was compared with 43 prior ethnomedicinal studies, conducted both nationally and in neighboring countries, and the results revealed that the Jaccard index (JI) ranged from 1.65 to 33.00. The highest degree of similarity (33.00) was found with another study conducted in Bangladesh, while the lowest degree of similarity (1.65) was found with a study conducted in Pakistan. This study recorded 12 new ethnomedicinal plant species, of which 6 have never been studied pharmacologically to date. CONCLUSIONS: This study showed that the Pangkhua community still depends substantially on ethnomedicinal plants for the treatment of various ailments and diseases and that several of these plants are used in novel ways or represented their first instances of use for medicinal applications.

Evaluation of anti-nociceptive and anti-inflammatory activities of the methanol extract of Holigarna caustica (Dennst.) Oken leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds. AIM OF THE STUDY: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action. MATERIALS AND METHODS: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis. RESULTS: MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties. CONCLUSIONS: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.

Oyster mushroom functions as an anti-hyperglycaemic through phosphorylation of AMPK and increased expression of GLUT4 in type 2 diabetic model rats.

OBJECTIVES: Traditionally, mushrooms have been used to reduce hyperglycaemia. However, the mechanism underlying this effect has not yet been explored. AMP-activated protein kinase (AMPK) is known to reduce hyperglycaemia through an insulin-independent pathway. This study aimed to observe the effect of oyster mushroom powder (OMP) on phosphorylation of AMPK (p-AMPK) and expression of GLUT4 mRNA in diabetic model rats. METHODS: Long-Evans rats were used to develop type 2 diabetic model rats through intraperitoneal induction of streptozotocin (STZ). OMP was supplemented at 5% with the usual feed of rats for 8 consecutive weeks. Then, the rats were sacrificed. RNA was extracted by the TRIzol reagent, and proteins were extracted from different tissues with RIPA lysis buffer. Expression of GLUT4 mRNA was measured through cDNA-PCR techniques, and p-AMPK was detected using western blotting. The band intensities of the PCR products and proteins were measured using Image J software. RESULTS: Supplementation of OMP for 8 weeks resulted in a reduction of the serum glucose level in STZ-induced, type 2 diabetic model rats. The levels of p-AMPK, as a ratio relative to ß-actin, increased in the muscle and adipose tissues of mushroom-treated type 2 diabetic model rats, compared to those in control diabetic model rats. Expression of GLUT4, as a ratio relative to GAPDH, increased significantly in both the muscle and adipose tissues of mushroom-treated diabetic rats. CONCLUSION: Oyster mushroom may decrease hyperglycaemia through increased p-AMPK and also expression of GLUT4 in the muscle and adipose tissues.