Synthesis and potential antidiabetic and lipid-lowering activities of putative asperidine B and its desmethyl analogue.

Putative asperidine B is an unnatural 2,6-disubstituted piperidin-3-ol and a structural isomer of (+)-preussin, a well-known pyrrolidin-3-ol alkaloid. This work reports the first enantioselective synthesis of putative asperidine B and its desmethyl analogue via a chiron approach starting from d-isoascorbic acid as well as evaluation of their free-radical scavenging, antidiabetic, and anti-hyperlipidemic activities. Both putative asperidine B and its desmethyl analogue markedly reduced the total reactive oxygen species (ROS) without cytotoxicity in hepatocellular carcinoma (HepG2) cells. The desmethyl analogue was a potent inducer for two antioxidant gene expression, glutathione peroxidase and superoxide dismutase, whereas putative asperidine B only induced superoxide dismutase. In addition, putative asperidine B exerted potent antidiabetic activity via α-glucosidase inhibition (IC50 = 0.143 ± 0.001 mg/mL) comparable to that of acarbose, an antidiabetic drug. Consistent with the parent asperidine B (preussin), both putative asperidine B and its desmethyl analogue inhibited cholesterol absorption in the intestinal Caco-2 cells. These novel and promising antioxidant, antidiabetic, and lipid-lowering effects of piperidin-3-ols could offer a starting point for this class of compounds for obesity and diabetic drug discovery.

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications.

Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.

Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle.

Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 µM) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl2, acetylcholine, Nω-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca2+ channel and is associated with K+ channels and muscarinic receptor, possibly by affecting non-selective cation channels and/or releasing intracellular calcium.

Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis.

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5,048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95%CIs 0.51-0.89, P = 0.005) without evidence of heterogeneity (I2= 0%, P = 0.629). Similarly, in three cohort studies with 2,223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95%CIs 0.35-0.77, P = 0.001) with very low evidence of heterogeneity (I2 = 3%, P = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49-0.77, P = 0.003) without heterogeneity (I2= 0%, P = 0.554). There were no obvious publication biases (Egger's test (P = 0.138) and Begg's test (P = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

Antidiabetic and Renoprotective Effects of Coffea arabica Pulp Aqueous Extract through Preserving Organic Cation Transport System Mediated Oxidative Stress Pathway in Experimental Type 2 Diabetic Rats.

Coffea arabica pulp (CP) is a by-product of coffee processing. CP contains polyphenols that have exhibited beneficial effects, including antioxidant and lipid-lowering effects, as well as enhanced insulin sensitivity, in in vitro and in vivo models. How polyphenols, as found in CP aqueous extract (CPE), affect type 2 diabetes (T2D) has not been investigated. Thus, the present study examined the potential antidiabetic, antioxidant, and renoprotective effects of CPE-rich polyphenols, using an experimental model of T2D in rats induced by a high-fat diet and a single low dose of streptozotocin. The T2D rats received either 1000 mg/kg body weight (BW) of CPE, 30 mg/kg BW of metformin (Met), or a combination treatment (CPE + Met) for 3 months. Plasma parameters, kidney morphology and function, and renal organic transport were determined. Significant hyperglycemia, hypertriglyceridemia, insulin resistance, increased renal lipid content and lipid peroxidation, and morphological kidney changes related to T2D were restored by both CPE and CPE + Met treatments. Additionally, the renal uptake of organic cation, 3H-1-methyl-4-phenylpyridinium (MPP+), was reduced in T2D, while transport was restored by CPE and CPE + Met, through an up-regulation of antioxidant genes and protein kinase Cα deactivation. Thus, CPE has antidiabetic and antioxidant effects that potentially ameliorate kidney function in T2D by preserving renal organic cation transport through an oxidative stress pathway.

Tiliacora triandra (Colebr.) Diels Leaf Aqueous Extract Inhibits Hepatic Glucose Production in HepG2 Cells and Type 2 Diabetic Rats.

This study investigated the effects of Tiliacora triandra (Colebr.) Diels aqueous extract (TTE) on hepatic glucose production in hepatocellular carcinoma (HepG2) cells and type 2 diabetic (T2DM) conditions. HepG2 cells were pretreated with TTE and its major constituents found in TTE, epicatechin (EC) and quercetin (QC). The hepatic glucose production was determined. The in vitro data were confirmed in T2DM rats, which were supplemented daily with 1000 mg/kg body weight (BW) TTE, 30 mg/kg BW metformin or TTE combined with metformin for 12 weeks. Results demonstrate that TTE induced copper-zinc superoxide dismutase, glutathione peroxidase and catalase genes, similarly to EC and QC. TTE decreased hepatic glucose production by downregulating phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and increasing protein kinase B and AMP-activated protein kinase phosphorylation in HepG2 cells. These results correlated with the antihyperglycemic, antitriglyceridemic, anti-insulin resistance, and antioxidant activities of TTE in T2DM rats, similar to the metformin and combination treatments. Consistently, impairment of hepatic gluconeogenesis in T2DM rats was restored after single and combined treatments by reducing PEPCK and G6Pase genes. Collectively, TTE could potentially be developed as a nutraceutical product to prevent glucose overproduction in patients with obesity, insulin resistance, and diabetes who are being treated with antidiabetic drugs.

Spirogyra neglecta Aqueous Extract Attenuates LPS-Induced Renal Inflammation.

Spirogyra neglecta (SN), commonly named "Tao" in Thai, is a genus of filamentous green macroalgae. SN contains polyphenols such as isoquercetin, catechin, hydroquinone and kaempferol. These constituents exhibit beneficial effects including anti-oxidant, anti-gastric ulcer, anti-hyperglycaemia and anti-hyperlipidaemia in both in vitro and in vivo models. Whether SN extract (SNE) has an anti-inflammatory effect in vivo remains unclear. This study examined the effect of SNE on renal function and renal organic transport in lipopolysaccharide (LPS)-induced renal inflammation in rats. Rats were randomised and divided into normal saline (NS), NS supplemented with 1000 mg/kg body weight (BW) of SNE (NS + SNE), intraperitoneally injected with 12 mg/kg BW of LPS and LPS treated with 1000 mg/kg BW of SNE (LPS + SNE). Biochemical parameters in serum and urine, lipid peroxidation concentration, kidney function and renal organic anion and cation transports were determined. LPS-injected rats developed renal injury and inflammation by increasing urine microalbumin, total malondialdehyde (MDA) and inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß protein expression, respectively. In addition, uptake of renal organic anion, [3H]-oestrone sulphate (ES), was reduced in LPS-injected rats together with increased expression of organic anion transporter 3 (Oat3). However, the renal injury and inflammation, as well as impaired Oat3 function and protein expression, were restored in LPS + SNE rats. Accordingly, SNE could be developed as nutraceutical product to prevent inflammation-induced nephrotoxicity.

Asperidines A-C, pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178.

One new pyrrolidine derivative, asperidine A (1), and two new piperidine derivatives, asperidines B (2) and C (3), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178 together with two known alkaloids. Compound 3 possessed an unprecedented 7-oxa-1-azabicyclo[3.2.1]octane skeleton with four chiral centers. Their structures were determined by spectroscopic evidence. The absolute configurations of compounds 2 and 3 were established using Mosher's method and further confirmed for compound 3 by X-ray crystallographic data. Compound 2 dose-dependently inhibited the CFTR-mediated chloride secretion in T84 cells with an IC50 value of 0.96 µM whereas 3 displayed the same activity with the IC50 value of 58.62 µM. Compounds 2 and 3 also significantly reduced intracellular ROS under both normal and H2O2-treated conditions compared with their respective controls in a dose-dependent manner without cytotoxic effect on Caco-2 cells. In addition, compound 3 was inactive against noncancerous Vero cells whereas compound 2 was considered to be inactive with the IC50 value of >10 µM.

Lovastatin Analogues from the Soil-Derived Fungus Aspergillus sclerotiorum PSU-RSPG178.

Three new lovastatin analogues (1, 4, and 5) together with four known lovastatin derivatives, namely, lovastatin (2), α,ß-dehydrolovastatin (3), α,ß-dehydrodihydromonacolin K (6), and α,ß-dehydro-4a,5-dihydromonacolin L (7), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound 5 exhibited the most potent activity against HMG-CoA reductase, with an IC50 value of 387 µM. In addition, the present study indicated the direct interaction of compound 5 with HMG-CoA reductase. Compound 5 was considered to be noncytotoxic against noncancerous Vero cells, with an IC50 value of 40.0 µM, whereas compound 2 displayed much stronger activity, with an IC50 value of 2.2 µM.

Antispasmodic Activity of Light-Roasted Coffee Extract and Its Potential Use in Gastrointestinal Motility Disorders.

Antispasmodic agents are crucial in managing gastrointestinal motility disorders by modulating muscle contractions and reducing symptoms like cramping and diarrhea. This study investigated the antispasmodic potential of different coffee bean extracts, including light coffee (LC), medium coffee (MC), and dark coffee (DC), on ileum contractions induced by potassium chloride (KCl), and elucidated their mechanisms of action using in vitro isolated tissue techniques. The results demonstrated that all coffee extracts reduced spontaneous contractions of rat ileum tissue in a dose-dependent manner. Among these, LC showed the most significant reduction in ileum contractions, particularly at higher concentrations. The key findings reveal that LC at 5 mg/mL significantly reduced CaCl2-induced contractions in isolated rat ileum tissue, indicating that LC may inhibit calcium influx or interfere with calcium signaling pathways. The presence of nifedipine, propranolol, and N-nitro-L-arginine methyl ester (L-NAME) have been confirmed in their involvement; they block calcium influx and calcium channels and activate ß-adrenergic pathways as part of LC's mechanism of action. The presence of their active compounds, particularly chlorogenic acid and caffeine, likely contributes to the observed antispasmodic effects. These findings suggest that LC exerts its antispasmodic effects by targeting key mechanisms involved in muscle spasms and intestinal motility, providing a potential for managing such conditions.

Suppressive Effect of Coffee Leaves on Lipid Digestion and Absorption In Vitro.

BACKGROUND: Coffee leaves are a major source of bioactive components and are used as ethnomedicine. However, despite their traditional medicinal use, information about their effects on antihyperlipidemia remains limited. METHODS: The aims of this study were to evaluate the main components of leaf extracts from Arabica and Robusta coffees and to examine the potential of these coffee leaves in reducing lipid digestion and absorption in vitro. RESULTS: Coffee leaf extracts from Arabica coffee contain a high amount of caffeine, whereas extracts from Robusta coffee contain high amounts of chlorogenic acid (CGA) and caffeine. Additionally, leaf extracts from Arabica and Robusta coffee demonstrated the inhibition of pancreatic lipase, decreased micellar cholesterol solubility, and reduced bile acid binding. Furthermore, these extracts resulted in a reduction in cholesterol uptake in Caco-2 cells. Molecular docking experiments supported this discovery, showing CGA and caffeine binding to Niemann-Pick C1-like 1 (NPC1L1), a key protein in cholesterol absorption. The results indicated that CGA and caffeine can competitively bind to NPC1L1 at the cholesterol binding pocket, reducing its cholesterol binding rate. These findings suggest that coffee leaves might help suppress lipid absorption and digestion, highlighting their potential use in preventing and treating hyperlipidemia.

Chlorogenic acid in green bean coffee on body weight: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Supplemental green bean coffee extract (GBCE) with caffeine has been shown to prevent weight gain. There are different dosages of GBCE that contain chlorogenic acid (CGA), and the data for their effectiveness in preventing weight gain (500 mg/day) is currently out of date. To better understand the effects of GBCE containing CGA on body weight, the present study sets out to perform a systematic review and meta-analysis of these studies. METHODS: Using electronic databases, including Scopus, Embase, PubMed, and Cochrane Library databases, literature was searched up to October 13, 2022. For the meta-analysis examining the impact of GBCE containing CGA (500 mg/day) on body weight with a random-effects model, the randomized controlled trials (RCTs) were considered. We calculated weighted mean differences and 95% confidence intervals (CIs). To gauge study heterogeneity, the Cochran Q statistic and I-squared tests (I2) were employed. RESULTS: The meta-analysis includes three RCTs with 103 individuals (case = 51, control = 52). The combined findings of GBCE with CGA at least 500 mg/day result in body weight reduction (WMD: - 1.30 and 95% CI: - 2.07 to - 0.52, p = 0.001) without study heterogeneity (I2 = 0%, p = 0.904) and without publication bias estimated using Egger's and Begger's test (p = 0.752 and p = 0.602, respectively). CONCLUSIONS: According to the meta-analysis, GBCE with CGA 500 mg/day lowers body weight. Nevertheless, despite its limited sample size and short-term study, this study was successful. Long-term research on the effectiveness and safety of GBCE and CGA on body weight require more clinical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021254916.

Chlorogenic acid rich in coffee pulp extract suppresses inflammatory status by inhibiting the p38, MAPK, and NF-κB pathways.

Coffee pulp (CP) is a coffee byproduct that contains various active ingredients, namely, chlorogenic acid (CGA) and caffeine. These active compounds show several benefits, including antihyperlipidemia, antioxidants, and anti-inflammation. However, the anti-inflammatory properties of Coffea pulp extract (CPE) are unknown. This work determined the impact of CPE on lipopolysaccharide (LPS)-activated murine macrophage cells and the molecular mechanism behind this action. RAW 264.7 cells were exposed to varying doses of CPE with or without LPS. Inflammatory markers and their mechanism were studied. CPE therapy has been shown to suppress the synthesis of inflammatory cytokines and mediators, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1ß, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Finally, CPE inactivated the nuclear factor-kappa B (NF-κB) and MAPK signaling pathways. Consequently, CPE might be used as a nutraceutical to treat inflammation and its related disorders.

Restoring Ampicillin Sensitivity in Multidrug-Resistant Escherichia coli Following Treatment in Combination with Coffee Pulp Extracts.

Escherichia coli, particularly multidrug-resistant (MDR) strains, is a serious cause of healthcare-associated infections. Development of novel antimicrobial agents or restoration of drug efficiency is required to treat MDR bacteria, and the use of natural products to solve this problem is promising. We investigated the antimicrobial activity of dried green coffee (DGC) beans, coffee pulp (CP), and arabica leaf (AL) crude extracts against 28 isolated MDR E. coli strains and restoration of ampicillin (AMP) efficiency with a combination test. DGC, CP, and AL extracts were effective against all 28 strains, with a minimum inhibitory concentration (MIC) of 12.5-50 mg/ml and minimum bactericidal concentration of 25-100 mg/ml. The CP-AMP combination was more effective than CP or AMP alone, with a fractional inhibitory concentration index value of 0.01. In the combination, the MIC of CP was 0.2 mg/ml (compared to 25 mg/ml of CP alone) and that of AMP was 0.1 mg/ml (compared to 50 mg/ml of AMP alone), or a 125-fold and 500-fold reduction, respectively, against 13-drug resistant MDR E. coli strains. Time-kill kinetics showed that the bactericidal effect of the CP-AMP combination occurred within 3 h through disruption of membrane permeability and biofilm eradication, as verified by scanning electron microscopy. This is the first report indicating that CP-AMP combination therapy could be employed to treat MDR E. coli by repurposing AMP.

Antibacterial Activity of Coffea robusta Leaf Extract against Foodborne Pathogens.

The purpose of this study was to examine the phytochemical compounds and antibacterial activity of Coffea robusta leaf extract (RLE). The results indicated that chlorogenic acid (CGA) is a major component of RLE. The minimum inhibitory concentrations (MICs) of RLE against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella Typhimurium were 6.25, 12.5, 12.5, and 12.5 mg/ml, respectively. RLE effectively damages the bacterial cell membrane integrity, as indicated by the high amounts of proteins and nucleic acids released from the bacteria, and disrupts bacterial cell membrane potential and permeability, as revealed via fluorescence analysis. Cytotoxicity testing showed that RLE is slightly toxic toward HepG2 cells at high concentration but exhibited no toxicity toward Caco2 cells. The results from the present study suggest that RLE has excellent potential applicability as an antimicrobial in the food industry.

Botanical aspects, phytochemicals, and toxicity of Tamarindus indica leaf and a systematic review of antioxidant capacities of T. indica leaf extracts.

Oxidative stress is a condition occurs when there is the imbalance between prooxidants and free radicals. It involves in cellular metabolism, aging, and immune response. Recently oxidative stress has been proved about its beneficial roles in human body. However, long term oxidative stress and high concentration of free radicals can lead to negative effects on organs, systems, and physiological conditions. Prooxidant or antioxidant, therefore, is one of the most important choices for the prevention of these anomaly. Tamarindus indica is a medicinal plant that has been reported as a source of antioxidants. The plants' leaves possess antioxidant effects according to many studies. However, these results have not yet been systematically summarized. The present systematic review summarizes and discusses about the in vitro antioxidant capacities of T. indica leaves. The plants' description and morphology, elements and phytochemical constituents, total phenolic and flavonoids contents and toxicity are also summarized and discussed here.

Antimicrobial Activity of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) against Clinical Isolates of Multidrug-Resistant Vibrio cholerae.

The spread of multidrug-resistant (MDR) Vibrio cholerae necessitates the development of novel prevention and treatment strategies. This study aims to evaluate the in vitro antibacterial activity of green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) against MDR V. cholerae. First, MIC and MBC values were evaluated by broth microdilution techniques against 45 V. cholerae strains. The checkerboard assay was then used to determine the synergistic effect of EGCG and tetracycline. The pharmaceutical mode of action of EGCG was clarified by time-killing kinetics and membrane disruption assay. Our results revealed that all of the 45 clinical isolates were susceptible to EGCG, with MIC and MBC values in the range of 62.5-250 µg/mL and 125-500 µg/mL, respectively. Furthermore, the combination of EGCG and tetracycline was greater than either treatment alone, with a fractional inhibitory concentration index (FICI) of 0.009 and 0.018 in the O1 and O139 representative serotypes, respectively. Time-killing kinetics analysis suggested that EGCG had bactericidal activity for MDR V. cholerae after exposure to at least 62.5 µg/mL EGCG within 1 h. The mode of action of EGCG might be associated with membrane disrupting permeability, as confirmed by scanning electron microscopy. This is the first indication that EGCG is a viable anti-MDR V. cholerae treatment.

Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer.

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1-1 µM of dinactin suppresses cell growth through induction of the G0/G1 phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.

Cholesterol-Lowering Effects of Asperidine B, a Pyrrolidine Derivative from the Soil-Derived Fungus Aspergillus sclerotiorum PSU-RSPG178: A Potential Cholesterol Absorption Inhibitor.

Isolated secondary metabolites asperidine B (preussin) and asperidine C, produced by the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, were found to exhibit inhibitory effects against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and oxidative stress in an in vitro assay. Whether or not the known pyrrolidine asperidine B and the recently isolated piperidine asperidine C have lipid-lowering effects remains unknown. Thus, this study aimed to investigate the hypocholesterolemic effects of asperidines B and C and identify the mechanisms involved in using in vitro, ex vivo, and in vivo models. The results show that both compounds interfered with cholesterol micelle formation by increasing bile acid binding capacity, similar to the action of the bile acid sequestrant drug cholestyramine. However, only asperidine B, but not asperidine C, was found to inhibit cholesterol uptake in Caco-2 cells by up-regulating LXRα without changing cholesterol transporter NPC1L1 protein expression. Likewise, reduced cholesterol absorption via asperidine-B-mediated activation of LXRα was also observed in isolated rat jejunal loops. Asperidine B consistently decreases plasma cholesterol absorption, similar to the effect of ezetimibe in rats. Therefore, asperidine B, the pyrrolidine derivative, has therapeutic potential to be developed into a type of cholesterol absorption inhibitor for the treatment of hypercholesterolemia.

Impact of Pharmacist-Led Diabetes Self-Care Education on Patients With Type 2 Diabetes in Pakistan: A Randomized Controlled Trial.

Introduction: There is a little evidence on efficacy of pharmacy-based interventions on clinical outcomes of type 2 diabetes mellitus (T2DM) patients in Pakistan. Objective: To appraise the impact of pharmacist-led self-care education on glycemic control, self-care practices and disease knowledge of T2DM patients with poor glycemic control (HbA1c ≥ 7%). Methods: In this 6-months, randomized controlled trial (RCT), n = 75, T2DM patients seeking care at a diabetes clinic were randomized in to two groups. Intervention group (n = 38) received two face-to-face educational sessions (at enrollment and on week 12), whereas control group (n = 37) received usual care. Outcome measures such as glycemic control, self-care practices and disease knowledge were assessed at the time of enrollment and after 6-months in both groups. Results: Thirty-three intervention and thirty-three participants from the control group completed the study. Mean glycated hemoglobin (% HbA1c) significantly reduced in the intervention group from 9.00 ± 1.43 to 8.09 ± 1.16 (p < .01). However, no significant change was observed in the control group (9.20 ± 1.24 to 8.93 ± .97; p = .06). Cohen's d effect size of the intervention on HbA1c was .78. Percentage of participants achieving glycemic control (HbA1c < 7%) were significantly higher (p < .05) in the intervention group as compared to the control group (twenty-four vs. six), after 6 months of the trial. A significant (p < .01) improvement in mean scores for disease knowledge and self-care activities was also observed in the intervention group participants, whereas no significant improvements (p > .05) were observed in the control group. Conclusion: The study demonstrated an improvement in glycemic control, disease knowledge and self-care activities of T2DM patients who received pharmacist-led educational intervention. The study findings support clinical significance of integrating pharmacy-based interventions in diabetes management.