Neuroprotective Effects of Black Pepper and Its Bioactive Compounds in Age-Related Neurological Disorders.

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders whose risk increases with age. The main pathological hallmarks of ANDs include behavioral changes, excessive oxidative stress, progressive functional declines, impaired mitochondrial function, protein misfolding, neuroinflammation, and neuronal cell death. Recently, efforts have been made to overcome ANDs because of their increased age-dependent prevalence. Black pepper, the fruit of Piper nigrum L. in the family Piperaceae, is an important food spice that has long been used in traditional medicine to treat various human diseases. Consumption of black pepper and black pepper-enriched products is associated with numerous health benefits due to its antioxidant, antidiabetic, anti-obesity, antihypertensive, anti-inflammatory, anticancer, hepatoprotective, and neuroprotective properties. This review shows that black pepper's major bioactive neuroprotective compounds, such as piperine, effectively prevent AND symptoms and pathological conditions by modulating cell survival signaling and death. Relevant molecular mechanisms are also discussed. In addition, we highlight how recently developed novel nanodelivery systems are vital for improving the efficacy, solubility, bioavailability, and neuroprotective properties of black pepper (and thus piperine) in different experimental AND models, including clinical trials. This extensive review shows that black pepper and its active ingredients have therapeutic potential for ANDs.

Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits.

Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Dioscorea nipponica Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that Dioscorea nipponica rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF.

Biological evidence of gintonin efficacy in memory disorders.

Gintonin is a novel glycolipoprotein, which has been abundantly found in the root of Korean ginseng. It holds lysophosphatidic acids (LPAs), primarily identified LPA C18:2, and is an exogenous agonist of LPA receptors (LPARs). Gintonin maintains blood-brain barrier integrity, and it has recently been studied in several models of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Gintonin demonstrated neuroprotective activity by providing action against neuroinflammation-, apoptosis- and oxidative stress-mediated neurodegeneration. Gintonin showed an emerging role as a modulator of synaptic transmission and neurogenesis and also potentially regulated autophagy in primary cortical astrocytes. It also ameliorated the toxic agent-induced and genetic models of cognitive deficits in experimental NDDs. As a novel agonist of LPARs, gintonin regulated several G protein-coupled receptors (GPCRs) including GPR40 and GPR55. However, further study needs to be investigated to understand the underlying mechanism of action of gintonin in memory disorders.

Therapeutic Potential of Lindera obtusiloba: Focus on Antioxidative and Pharmacological Properties.

Lindera obtusiloba (LO) BLUME from the genus Lindera (Lauraceae) is a medicinal herb traditionally used in Southeast Asian countries. Indigenously, extracts of different parts of the plant have been used to improve blood circulation and treat allergy, inflammation, rheumatism, and liver diseases. LO is a rich source of therapeutically beneficial antioxidative phytochemicals, such as flavonoids, butenolides, lignans and neolignans. Moreover, recent studies have unravelled the pharmacological properties of several newly found active constituents of LO, such as anti-inflammatory antioxidants (+)-syringaresinol, linderin A, anti-atherosclerotic antioxidant (+)-episesamin, anti-melanogenic antioxidants quercitrin and afzelin, cytotoxic 2-(1-methoxy-11-dodecenyl)-penta-2,4-dien-4-olide, (2Z,3S,4S)-2-(11-dodecenylidene)-3-hydroxy-4-methyl butanolide, anti-allergic koaburaside, (6-hydroxyphenyl)-1-O-beta-d-glucopyranoside and 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-d-glucopyranoside and the antiplatelet-activity compound Secolincomolide A. These findings demonstrate that LO can be a potential source of antioxidants and other prospective therapeutically active constituents that can lead to the development of oxidative stress-mediated diseases, such as cardiovascular disorders, neurodegenerative disorders, allergies, inflammation, hepatotoxicity, and cancer. Here, the antioxidant properties of different species of Lindera genus are discussed briefly. The traditional use, phytochemistry, antioxidative and pharmacological properties of LO are also considered to help researchers screen potential lead compounds and design and develop future therapeutic agents to treat oxidative stress-mediated disorders.

Evaluation of carbon tetrachloride fraction of Actinodaphne angustifolia Nees (Lauraceae) leaf extract for antioxidant, cytotoxic, thrombolytic and antidiarrheal properties.

Actinodaphne angustifolia Nees (Family: Lauraceae) is commonly used in folk medicine against urinary disorder and diabetes. The objective of the present study was to evaluate the antioxidant, cytotoxic, thrombolytic, and antidiarrheal activities of carbon tetrachloride (CCl4) fraction of leaves of A. angustifolia (CTFAA) in different experimental models. Antioxidant activity was evaluated by using qualitative and quantitative assays, while antidiarrheal effects assessed with castor oil-induced diarrheal models in mice. The clot lysis and brine shrimp lethality bioassay were used to investigate the thrombolytic and cytotoxic activities, respectively. CTFAA showed antioxidant effects in all qualitative and quantitative procedures. The fraction produced dose-dependent and significant (P<0.05 and P<0.01) activities in castor oil-induced diarrheal models. Moreover, CTFAA significantly (P<0.05) demonstrated a 15.29% clot lysis effect in the thrombolytic test, and the brine shrimp lethality assay LC50 value was 424.16 µg/ml bioassay. In conclusion, the current study showed CTFAA has significant antidiarrheal effects along with modest antioxidant and thrombolytic effects, and these data warrant further experiment to justify and include CTFAA as a supplement to mitigate the onset of diarrheal and cardiovascular disease.

Anti-hyperglycaemic activity of H. rosa-sinensis leaves is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of insulin secretion.

ETHNOPHARMACOLOGICAL RELEVANCE: Hibiscus rosa-sinensis (HRS) is a tropical flowery plant, widely distributed in Asian region and an important traditional medicine used in many diseases including cough, diarrhoea and diabetes. AIM OF THIS STUDY: Hibiscus rosa-sinensis (HRS) leaves have been reported to possess anti-hyperglycaemic activity, but little is known concerning the underlying mechanism. This study investigated effects of ethanol extract of HRS on insulin release and glucose homeostasis in a type 2 diabetic rat model. MATERIALS & METHODS: Effects of ethanol extract of grinded H. rosa-sinensis (HRS) leaves on insulin release, membrane potential and intracellular calcium were determined using rat clonal ß-cells (BRIN-BD11 cells) and isolated mouse pancreatic islets. Effects on DPP-IV enzyme activity were investigated in vitro. Acute effects of HRS on glucose tolerance, gut perfusion in situ, sucrose content, intestinal disaccharidase activity and gut motility were measured. Streptozotocin induced type 2 diabetic rats treated for 28 days with ethanol extract of HRS leaf (250 and 500 mg/kg) were used to assess glucose homeostasis. RESULTS: HRS, significantly increased insulin release from clonal rat BRIN-BD11 cells and this action was confirmed using isolated mouse pancreas islets with stimulatory effects equivalent to GLP-1. HRS induced membrane depolarization and increased intracellular Ca2+ in BRIN BD11 cells and significantly inhibited DPP-IV enzyme activity in vitro. HRS administration in vivo improved glucose tolerance in type 2 diabetic rats, inhibited both glucose absorption during gut perfusion and postprandial hyperglycaemia and it reversibly increased unabsorbed sucrose passage through the gut following sucrose ingestion. HRS decreased intestinal disaccharidase activity and increased gastrointestinal motility in non-diabetic rats. In a chronic 28-day study with type 2 diabetic rats, HRS, at 250 or 500 mg/kg, significantly decreased serum glucose, cholesterol, triglycerides and increased circulating insulin, HDL cholesterol and hepatic glycogen without increasing body weight. CONCLUSION: These data suggest the antihyperglycaemic activity of HRS is mediated by inhibiting carbohydrate digestion and absorption, while significantly enhancing insulin secretion in a dose dependent manner. This suggests that HRS has potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes.

Nigella sativa stimulates insulin secretion from isolated rat islets and inhibits the digestion and absorption of (CH2O)n in the gut.

Nigella sativa seeds are traditionally reputed as possessing anti-diabetic properties. As a result, we aim to explore the mechanism of its anti-hyperglycemic activity. The present study uses various experimental designs including gastrointestinal (GI) motility, intestinal disaccharidase activity and inhibition of carbohydrate digestion and absorption in the gut. The animals used as type 2 diabetic models were induced with streptozotocin to make them as such. Oral glucose tolerance test was performed to confirm that the animals were indeed diabetic. The extract reduced postprandial glucose, suggesting it interfered with glucose absorption in the gut. It also improved glucose (2.5g/kg, b/w) tolerance in rats. Furthermore, treatment with N. sativa produced a significant improvement in GI motility, while reduced disaccharidase enzyme activity in fasted rats. The extract produced a similar effect within an acute oral sucrose (2.5g/kg, b/w) load assay. Following sucrose administration, a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract. This indicates that N. sativa has the potentiality to liberate GI content and reduce or delay glucose absorption. A potential hypoglycemic activity of the extract found in insulin release assay, where the extract significantly improved insulin secretion from isolated rat islets. These concluded present findings give rise to the implication that N. sativa seeds are generating postprandial anti-hyperglycemic activity within type 2 diabetic animal models via reducing or delaying carbohydrate digestion and absorption in the gut as well as improving insulin secretion in response to the plasma glucose.

Anti-hyperglycaemic activity of Moringa oleifera is partly mediated by carbohydrase inhibition and glucose-fibre binding.

Moringa oleifera has potential anti-hyperglycaemic effects that have been reported earlier by different scientific groups using animal models of diabetes. We aimed to explore the possible mechanisms of action of M. oleifera extract through different methods. Primarily, we measured fasting blood glucose and performed glucose tolerance test, in Type 2 diabetic rats. Further, we studied the effects of extracts on pancreatic insulin concentration. Extracts' effect on carbohydrate breakdown was assayed using α-amylase inhibition assays and assay of six different segments of gastrointestinal (GI) tracts. An in situ intestinal perfusion model and a glucose fibre assay were performed to see the potentiality of M. oleifera on glucose absorption. M. oleifera showed no significant change in insulin secretion in vivo Additionally, substantial effect of the extract was seen on retarded glucose absorption and in the in situ perfusion study of rat intestinal model. α-amylase action was inhibited by the extract, yet again, these findings were further confirmed via the Six Segment assay, where sucrose digestion was found to be inhibited throughout the length of the GI tract. A combined in vitro, in vivo and in situ tests justified the potential of anti-hyperglycaemic activity of M. oleifera and its tissue level mechanism is also justified.

Investigation of antinociceptive activity of methanolic extract of Persicaria orientalis leaves in rodents.

BACKGROUND: This study aims to evaluate the scientific basis of traditional application of Persicaria orientalis for reducing pain and inflammation. METHODS: An in vitro method was performed to investigate the presence of the anti-inflammatory activity of methanolic crude extract of P. orientalis. In addition, an in vivo study was conducted in which the hot-plate and tail immersion methods were applied to explore the acute effect of P. orientalis on analgesia. The potency to inhibit chronic inflammation in mice was justified by the carrageenan-induced paw edema and formalin-induced edema methods. For all in vivo testing in animal models (albino mice and rats), plant extract was given via the oral route at doses of 250 mg/kg and 500 mg/kg. RESULTS: The methanolic extract of P. orientalis produced a significant (p<0.001) inhibition of analgesia with a prolongation of pain response time by 61.80% at 500 mg/kg. The extract also exhibited a potential anti-inflammatory (56.99%) effect, which was also statistically significant (p<0.001). The present study suggests that the methanolic extract of P. orientalis has potential anti-inflammatory as well as analgesic activity and this extract is effective in the treatment of both acute and chronic pain. CONCLUSIONS: Our current study revealed pharmacological properties of the methanolic extract of P. orientalis and also gave a solid scientific platform against its traditional use. The protecting ability of P. orientalis against inflammatory stimuli may be due to phenolic or flavonoid compounds which we have found through phytochemical analysis.

Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark).

BACKGROUND: The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti-inflammatory and analgesic activity and phytochemical screening. METHODS: Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. RESULTS: One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%±0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89±0.079 min, whereas the compared standard's interval was 21.48±0.397 min. In tail immersion method, the pain threshold was 3.02±0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. CONCLUSIONS: This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent.