Channa striatus in inflammatory conditions: A systematic review.

Channa striatus (CS), or snakehead murrel, is an obligate air-breathing freshwater fish. Besides its wound healing properties, CS has also been reported to exhibit anti-inflammatory effects in multiple studies. While there are anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), their long-term use is associated with an increased risk of peptic ulcers, acute renal failure, stroke, and myocardial infarction. Thus, it is essential to look at natural methods such as CS extract. While there is an abundant number of investigative studies on the inflammatory properties of CS, the quality of these studies has not been evaluated effectively. Thus, this review aims to summarise, evaluate, and critically appraise currently available literature regarding the anti-inflammatory properties of CS extract. This is done by performing a search using four databases, namely Google Scholar, Embase via Elsevier, Scopus, and Web of Science, with the following terms: Channa striatus AND inflammation. From our review, CS has been experimentally shown to positively affect inflammatory conditions such as gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects were also found on inflammation in the presence of tuberculosis and in situations that involve inflammation, such as wound healing. While CS clearly has potential for treating inflammatory conditions, much work needs to be done on identifying and isolating the active constituents before exact mechanisms of action can be worked out to develop future anti-inflammatory medications.

A comprehensive phytochemical, biological, and toxicological studies of roots and aerial parts of Crotalaria burhia Buch.-Ham: An important medicinal plant.

This study was designed to seek the phytochemical analysis, antioxidant, enzyme inhibition, and toxicity potentials of methanol and dichloromethane (DCM) extracts of aerial and root parts of Crotalaria burhia. Total bioactive content, high-performance liquid chromatography-photodiode array detector (HPLC-PDA) polyphenolic quantification, and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis were utilized to evaluate the phytochemical composition. Antioxidant [including 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)], 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power assay (FRAP), cupric reducing antioxidant capacity CUPRAC, phosphomolybdenum, and metal chelation assays] and enzyme inhibition [against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, α-amylase, and tyrosinase] assays were carried out for biological evaluation. The cytotoxicity was tested against MCF-7 and MDA-MB-231 breast cell lines. The root-methanol extract contained the highest levels of phenolics (37.69 mg gallic acid equivalent/g extract) and flavonoids (83.0 mg quercetin equivalent/g extract) contents, and was also the most active for DPPH (50.04 mg Trolox equivalent/g extract) and CUPRAC (139.96 mg Trolox equivalent /g extract) antioxidant assays. Likewise, the aerial-methanol extract exhibited maximum activity for ABTS (94.05 mg Trolox equivalent/g extract) and FRAP (64.23 mg Trolox equivalent/g extract) assays. The aerial-DCM extract was noted to be a convincing cholinesterase (AChE; 4.01 and BChE; 4.28 mg galantamine equivalent/g extract), and α-glucosidase inhibitor (1.92 mmol acarbose equivalent/g extract). All of the extracts exhibited weak to modest toxicity against the tested cell lines. A considerable quantities of gallic acid, catechin, 4-OH benzoic acid, syringic acid, vanillic acid, 3-OH-4-MeO benzaldehyde, epicatechin, p-coumaric acid, rutin, naringenin, and carvacrol were quantified via HPLC-PDA analysis. UHPLC-MS analysis of methanolic extracts from roots and aerial parts revealed the tentative identification of important phytoconstituents such as polyphenols, saponins, flavonoids, and glycoside derivatives. To conclude, this plant could be considered a promising source of origin for bioactive compounds with several therapeutic uses.

Chemotherapeutic Role of Polyphenols Present in Ocimum sanctum.

Ocimum sanctum is a sacred herb of India and is commonly known as 'Tulsi' or 'Holy Basil' in regional languages of the country. Various parts of O. sanctum are recognised to have remarkable therapeutic efficacy, and are therefore used in Indian traditional medicine system, Ayurveda. Scientific studies have shown that O. sanctum has a range of pharmacological activities. The presence of a substantial amount of polyphenols in O. sanctum could be the reason for its excellent bioactivity. Polyphenols are used to prevent or treat oncologic diseases due to their anti-cancer effects, which are related to activation of apoptotic signaling, cell cycle arrest, binding ability with membrane receptors, and potential effects on immunomodulation and epigenetic mechanisms. The poor bioavailability of polyphenols restricts their clinical use. The application of nanonization has been implemented to improve their bioavailability, penetrability, and prolong their anticancer action. The present review analyses the recent preclinical studies related to the chemo-preventive and therapeutic potential of polyphenols present in O. sanctum. Moreover, the current article also examines in-depth the biochemical and molecular mechanisms involved in the antineoplastic actions of the considered polyphenols.

Nanoencapsulation of Polyphenols as Drugs and Supplements for Enhancing Therapeutic Profile - A Review.

Polyphenolic phytoconstituents have been widely in use worldwide for ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol, curcumin as nutritional supplements has been researched widely. The use of polyphenols and specifically quercetin, for improving memory and mental endurance has shown significant effects among rats. Even though similar results have not been resonated among humans, but preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to their free radical scavenging properties, anti-inflammatory, anti-cancer, and immunomodulatory effects. In- -spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and their application as drugs and supplements. Nanoformulations of natural polyphenols as bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin- 3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids, and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effects. However, the hindrances in their absorption, specificity, and bioavailability can be overcome using nanotechnology.

Multi-Platform Metabolomics Analyses Revealed the Complexity of Serum Metabolites in LPS-Induced Neuroinflammed Rats Treated with Clinacanthus nutans Aqueous Extract.

The use of metabolomics as a comprehensive tool in the analysis of metabolic profiles in disease progression and therapeutic intervention is rapidly advancing. Yet, a single analytical platform could not be applied to cover the entire spectrum of a biological sample's metabolome. In the present paper, multi-platform metabolomics approaches were explored to determine the diverse rat sera metabolites extracted from intracerebroventricular lipopolysaccharides (LPS)-induced neuroinflammed rats treated with oral therapeutic interventions of positive drug (dextromethorphan, 5 mg/kg BW); with Clinacanthus nutans (CN) aqueous extract (CNE, 500 mg/kg BW); and with phosphate buffer saline (PBS) as the control group for 14 days. Analyzed by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) techniques, this study depicted the potential of metabolites associated with neuroinflammation and verified by MetDisease. The key observations in the perturbed metabolic pathways that showed ameliorative effects were linked to the class of amino acid and peptide metabolism involving valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Lipid metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, terpenoid backbone biosynthesis, and glycosphingolipid metabolism were also affected. Current findings suggested that the putative biomarkers, especially lysophosphatidic acid (LPA) and 5-diphosphomevalonic acid from glycerophospholipid and squalene/terpenoid and cholesterol biosynthesis, respectively, showed the ameliorative effects of the drug and CN treatments by controlling cell differentiation and proliferation. Our study proved that the complex and dynamic sera profiling affected during the CN treatment was greatly influenced by the analytical platform selection as integration between the two data yielded a more holistic summary of the metabolite pattern changes. Hence, an evidence-based herb, such as CN, can be used for novel diagnostic tools in the quest for ethnopharmacological studies.

Protective Effect of Natural Products against Huntington's Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action.

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.

Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics.

Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.

The anti-neuroinflammatory effects of Clinacanthus nutans leaf extract on metabolism elucidated through 1H NMR in correlation with cytokines microarray.

Clinacanthus nutans (CN) (Acanthaceae) is well-known for its anti-inflammatory properties among Asian communities; however, there are currently no data specifically focused on the anti-inflammatory effects of CN on the brain tissue. Neuroinflammation is a common consequence of toxin intrusion to any part of the central nervous system (CNS). As an innate immune response, the CNS may react through both protective and/or toxic actions due to the activation of neuron cells producing pro- and/or anti-inflammatory cytokines in the brain. The unresolved activation of the inflammatory cytokines' response is associated with the pathogenesis of neurological disorders. The present study aimed to decipher the metabolic mechanism on the effects of 14 days oral treatment with CN aqueous extract in induced-lipopolysaccharides (LPS) rats through 1H NMR spectroscopic biomarker profiling of the brain tissue and the related cytokines. Based on the principal component analysis (PCA) of the nuclear magnetic resonance (NMR) spectral data, twenty-one metabolites in the brain tissue were profiled as biomarkers for the LPS (10 µL)-induced neuroinflammation following intracerebroventricular injection. Among the twenty-one biomarkers in the neuroinflammed rats, CN treatment of 1000 and 500 mg/kg BW successfully altered lactate, pyruvate, phosphorylcholine, glutamine, and α-ketoglutarate when compared to the negative control. Likewise, statistical isolinear multiple component analysis (SIMCA) showed that treatments by CN and the positive control drug, dextromethorphan (DXM, 5 mg/kg BW), have anti-neuroinflammatory potential. A moderate correlation, in the orthogonal partial least squares (OPLS) regression model, was found between the spectral metabolite profile and the cytokine levels. The current study revealed the existence of high levels of pro-inflammatory cytokines, namely IL-1α, IL-1ß, and TNF-α in LPS-induced rats. Both CN dose treatments lowered IL-1ß significantly better than DXM Interestingly, DXM and CN treatments both exhibited the upregulation of the anti-inflammatory cytokines IL-2 and 4. However, DXM has an advantage over CN in that the former also increased the expression of IL-10 of anti-inflammatory cytokines. In this study, a metabolomics approach was successfully applied to discover the mechanistic role of CN in controlling the neuroinflammatory conditions through the modulation of complex metabolite interactions in the rat brain.

Potential Neuroprotective Effect of the HMGB1 Inhibitor Glycyrrhizin in Neurological Disorders.

Glycyrrhizin (glycyrrhizic acid), a bioactive triterpenoid saponin constituent of Glycyrrhiza glabra, is a traditional medicine possessing a plethora of pharmacological anti-inflammatory, antioxidant, antimicrobial, and antiaging properties. It is a known pharmacological inhibitor of high mobility group box 1 (HMGB1), a ubiquitous protein with proinflammatory cytokine-like activity. HMGB1 has been implicated in an array of inflammatory diseases when released extracellularly, mainly by activating intracellular signaling upon binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). HMGB1 neutralization strategies have demonstrated disease-modifying outcomes in several preclinical models of neurological disorders. Herein, we reveal the potential neuroprotective effects of glycyrrhizin against several neurological disorders. Emerging findings demonstrate the therapeutic potential of glycyrrhizin against several HMGB1-mediated pathological conditions including traumatic brain injury, neuroinflammation and associated conditions, epileptic seizures, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Glycyrrhizin's effects in neurological disorders are mainly attributed to the attenuation of neuronal damage by inhibiting HMGB1 expression and translocation as well as by downregulating the expression of inflammatory cytokines. A large number of preclinical findings supports the notion that glycyrrhizin might be a promising therapeutic alternative to overcome the shortcomings of the mainstream therapeutic strategies against neurological disorders, mainly by halting disease progression. However, future research is warranted for a deeper exploration of the precise underlying molecular mechanism as well as for clinical translation.

Ethanolic Extract of Orthosiphon stamineus Improves Memory in Scopolamine-Induced Amnesia Model.

Alzheimer's disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning. Orthosiphon stamineus (OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties whereby in vitro studies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kg via oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.

Effects of Clinacanthus nutans leaf extract on lipopolysaccharide -induced neuroinflammation in rats: A behavioral and 1H NMR-based metabolomics study.

OBJECTIVE: This research revealed the biochemical outcomes of metabolic dysregulation in serum associated with physiological sickness behavior following lipopolysaccharide (LPS)-induced neuroinflammation in rats, and treatment with Clinacanthus nutans (CN). Verification of 1H NMR analysis of the CN aqueous extract proved the existence of bioactive phytochemical constituents' in extract. MATERIALS AND METHODS: Twenty-five rats were subjected to unilateral stereotaxic injection of 10 µL LPS (1 mg/mL), while another ten rats were injected with phosphate-buffered saline (PBS, 10 µL) as control. Then, 29 parameters of rat behavior related to sickness were tracked by a device software (SMART 3.0.1) on days 0 and 14 of CN treatment. The acquired and accumulated data were analyzed using multivariate data analysis with the SIMCA Software package (version 13, Umetrics AB; Umeå, Sweden). The pattern trends of related groups were documented using PCA and OPLS analysis. RESULTS: A similar ameliorated correlation pattern was detected between improvement in physiological sickness behavior and anti-inflammatory biomarkers by the 1H NMR spectra of the sera following treatment with CN (500 and 1000 mg/kg body weight (bw)) and the control drug (dextromethorphan hydrobromide, 5 mg/kg of rats bw) in rats. Here, 21 biomarkers were detected for neuroinflammation. Treatment with the aqueous CN extract resulted in a statistically significant alteration in neuroinflammation metabolite biomarkers, including ethanol, choline, and acetate. CONCLUSION: This result denotes that the metabolomics approach is a reliable tool to disclose the relationship between central neuroinflammation, and systemic metabolic and physiological disturbances which could be used for future ethno-pharmacological assessments.

Plant Derived Phytocompound, Embelin in CNS Disorders: A Systematic Review.

A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.

Anticonvulsant screening of luteolin in four mouse seizure models.

Luteolin, a common plant polyphenolic flavonoid, has antioxidant, neuroprotective, anxiolytic and anti-inflammatory properties, which led us to hypothesize that luteolin is anticonvulsant. Here, we evaluated the effects of acute and chronic luteolin injection (i.p.) in four mouse seizure models, the 6 Hz model, maximal electroshock test (MEST), pentylenetetrazole (PTZ) and second hit PTZ test in the chronic stage of the pilocarpine model. Using real-time PCR mRNA levels of toll like receptor 4 (Tlr4), were quantified in the pilocarpine model, because luteolin has been shown to block the downstream signaling of TLR4. Luteolin did not exhibit any consistent anti- or pro-convulsant actions after single dosing in the 6 Hz (0.3-10 mg/kg), MEST (0.3-20 mg/kg) and PTZ (3 mg/kg) tests, nor after repeated daily dosing (10 mg/kg) in the 6 Hz model. Tlr4 mRNA levels were upregulated 3 days after pilocarpine-induced status epilepticus (SE), but unaltered at three weeks in the chronic stage of the model. At that time, there was no effect of repeated luteolin injections (10 mg/kg, i.p.) in the second hit PTZ test, indicating that TLR-4 signaling may be not one of the main players determining the seizure threshold in this seizure model. In summary, we found no indications that luteolin is pro- or anti-convulsant in one chronic and three acute mouse seizure models.