Edward James Johns

This is the first method to enable real-time, selective measurement of ARNA in unanesthetized rats without interference from efferent signals. The use of targeted lidocaine administration allows functional separation of afferent and efferent components of renal nerve activity in vivo. This technique provides a tool to study renorenal reflexes under physiological and pathophysiological conditions, advancing our understanding of autonomic regulation in health and disease.

Renal injury is associated with inflammatory responses within the kidney which could involve activation of transient receptor potential vanilloid 1 (TRPV1) channels. This study investigated whether TRPV1 channels modulate baroreflex regulation of renal sympathetic nerve activity (RSNA) in a rat model of cisplatin‐mediated renal injury. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA 4 days after a single i.p. dose of cisplatin (5 mg kg ⁻¹ ). RSNA and HR baroreflex gain curves (BRC) were generated and the decrease in RSNA to volume expansion was determined during intrarenal capsazepine (CPZ, 15 µg kg ⁻¹ h ⁻¹ ) infusion. In the cisplatin group (MAP: 85 ± 13 mmHg; HR: 328 ± 17 bpm; RSNA: 0.83 ± 0.41 µV s), the slope and maximum gain of the BRC were approximately 50% lower ( P = 0.015–0.033) than the control group (MAP: 78 ± 12 mmHg; HR: 352 ± 27 bpm; RSNA: 0.57 ± 0.36 µV s). Intrarenal CPZ infusion in the cisplatin group restored the slope (0.15 ± 0.04 vs. 0.09 ± 0.02, P = 0.014) of the RSNA BRC to near normal values. The RSNA response to volume expansion in the cisplatin group was enhanced following CPZ compared to vehicle infusion (−24 ± 14% vs. 1.7 ± 39%, P = 0.015). Intrarenal tumour necrosis factor α (TNF‐α) infusion ( 2 µg kg ⁻¹ h ⁻¹ ) in normal rats decreased the slope of the BRC by 40% ( P = 0.035) compared to vehicle infusion, which was slightly enhanced following intrarenal CPZ infusion. These findings demonstrate that TRPV1 channels contribute to the depressed baroreceptor control of RSNA in renal injury. Furthermore, the action of TNF‐α in disrupting the baroreflex control mechanism partially involves TRPV1 channels.

Emerging investigations have indicated that many plant polysaccharides may be beneficial for treating metabolic diseases. To date, the therapeutic efficacy and potential toxicity of polysaccharides extracted from Clinacanthus nutans (C. nutans) remain unexplored. This study investigated the in vivo acute and subacute oral toxicological profiles of the highest doses of C. nutans bioactive polysaccharides (CNBP) extracted from the leaves using conventional toxicity methods. The total of 39 healthy 8–10 weeks male Sprague-Dawley rats (n = 3) were randomly assigned to control (C), acute (A) and subacute (SA) groups receiving 125, 250, 500, 1,000, 2,000 or 3,000 mg/kg/day of CNBP extract, respectively. The acute group received a single dose of CNBP extract, whereas the subacute group received daily single doses of CNBP extract for 14 days. Oral administration of up to 3,000 mg/kg CNBP extract caused no abnormal signs of toxicity during 14 days. However, daily administration of 500 mg/kg or higher doses of CNBP extract for 14 days induced a mild degree of toxicity in the liver, characterised by elevated alkaline phosphatase levels with C (163 ± 9 U/L) vs. SA500 (222 ± 49 U/L), SA1000 (223 ± 29 U/L), SA2000 (238 ± 33 U/L) and SA3000 (252 ± 18 U/L). CNBP extracts exhibit therapeutic potential, exemplified by diuretic, natriuretic, anti-hypertensive, anti-tachycardia, reno-protective and cholesterol-lowering properties. Precautions should be taken when administering the extracts at higher doses and for longer durations.

Dysregulation of lipid homeostasis contributes to obesity and can directly lead to several critical public health concerns globally. This paper aimed to present a brief review of related properties and the use of pancreatic lipase inhibitors as the future weight loss drug discovery and development procured from a wide range of natural sources. A total of 176 pancreatic lipase inhibitory peptides were identified from recent publications and peptide databases. These peptides were classified into three categories according to their peptide length and further analyzed using bioinformatic approaches to identify their structural activity relationship. Molecular docking analyses were conducted for each amino acid at the terminal position of the peptides to predict the binding affinity between peptide-enzyme protein complexes based on intermolecular contact interactions. Overall, the observations revealed the features of the inhibitory peptides and their inhibitory mechanisms and interactions. These findings strived to benefit scientists whose research may be relevant to anti-obesity drug development and/or discovery thereby support effective translation of preclinical research for humans’ health being.

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.

Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.

Background Oxidative stress, associates with metabolic and anthropometric perturbations, leads to reactive oxygen species production and decrease in plasma adiponectin concentration. We investigated pharmacodynamically the pathophysiological role and potential implication of exogenously administered adiponectin with full and partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists on modulation of oxidative stress, metabolic dysregulation and antioxidant potential in streptozotocin induced Spontaneously hypertensive rats (SHR).Methods Group I (WKY) serve as normotensive control, whereas 42 male SHRs were randomized equally into 7 groups (n = 6), group II: SHR control, groups III: SHR diabetic control, group IV, V and VI treated with irbesartan (30 mg/kg), pioglitazone (10 mg/kg) and adiponectin (2.5 µg/kg), whereas, groups VII and VIII received co-treatments as irbesartan + adiponectin), (pioglitazone + adiponectin) respectively. Diabetes was induced using an intra-peritoneal injection of Streptozotocin (40 mg/kg). Plasma adiponectin, lipid contents, arterial stiffness with oxidative stress bio-markers were measured using an in-vitro and in-vivo analysis.Results Diabetic SHRs exhibited hyperglycaemia, hypertriglyceridemia, hypercholesterolemia, increased arterial stiffness with reduced plasma adiponectin and antioxidant enzymatic levels (P < 0.05). Diabetic SHRs pre-treated with pioglitazone and adiponectin separately exerted improvements in antioxidant enzyme activities, abrogated arterial stiffness, offset the increased production of reactive oxygen species and dyslipidaemic effects of STZ, except for blood pressure values which were more pronounced with irbesartan treated groups (all P < 0.05).Conclusions The combined treatment of exogenously administered adiponectin with full PPAR-γ agonist augmented the improvement in lipid contents and adiponectin concentration, restores arterial stiffness with antioxidant potential effects, indicating degree of synergism between adiponectin and full PPAR-γ agonists (pioglitazone).