Clovamide and Its Derivatives-Bioactive Components of Theobroma cacao and Other Plants in the Context of Human Health.

Clovamide (N-caffeoyl-L-3,4-dihydroxyphenylalanine, N-caffeoyldopamine, N-caffeoyl-L-DOPA) is a derivative of caffeic acid, belonging to phenolamides (hydroxycinnamic acid amides). Despite a growing interest in the biological activity of natural polyphenolic substances, studies on the properties of clovamide and related compounds, their significance as bioactive components of the diet, as well as their effects on human health are a relatively new research trend. On the other hand, in vitro and in vivo evidence indicates the considerable potential of these substances in the context of maintaining human health or using them as pharmacophores. The name "clovamide" directly derives from red clover (Trifolium pratense L.), being the first identified source of this compound. In the human diet, clovamides are mainly present in chocolate and other cocoa-containing products. Furthermore, their occurrence in some medicinal plants has also been confirmed. The literature reports deal with the antioxidant, anti-inflammatory, neuroprotective, antiplatelet/antithrombotic and anticancer properties of clovamide-type compounds. This narrative review summarizes the available data on the biological activity of clovamides and their potential health-supporting properties, including prospects for the use of these compounds for therapeutic purposes.

UHPLC-MS/MS analysis and protective effects on neurodegenerative diseases of phenolic compounds in different parts of Diospyros kaki L. cv. Mopan.

Persimmon (Diospyros kaki L. cv. Mopan.), an important commercial crop belonging to the genus of Diospyros in the Ebenaceae family, is rich in bioactive phenolic compounds. In this study, the phenolic compounds from fruits, leaves, and calyces of persimmon were qualitatively and quantitatively determined by UPLC-Q-Exactive-Orbitrap/MS and UPLC-QqQ-MS/MS, respectively. Furthermore, the role of phenolic extract from different parts of persimmon on neuroprotective activity in vitro, through against oxidative stress and anti-neuroinflammation effect was firstly evaluated. The results showed that 75 phenolic compounds, and 3 other kinds of compounds were identified, among which 44 of phenolic compounds were quantified from different parts of persimmon. It is the first time that epicatechin-epigallocatechin, catechin-epigallocatechin, catechin-epigallocatechin (A-type), and glycoside derivatives of laricitrin were identified in persimmon extract. The dominated phenolic compounds in three parts of persimmon were significantly different. All phenolic extracts from each part of persimmon showed strong neuroprotective activities against H2O2-induced oxidative stress in PC-12 cells and LPS-induced BV2 cells. The fruit extract presented the strongest activity, followed by calyx and leaf extract. The systematic knowledge on the phytochemical composition along with activity evaluation of different parts of persimmon could contribute to their targeted selection and development.

Tetraselmis chuii Edible Microalga as a New Source of Neuroprotective Compounds Obtained Using Fast Biosolvent Extraction.

Tetraselmis chuii is an EFSA-approved novel food and dietary supplement with increasing use in nutraceutical production worldwide. This study investigated the neuroprotective potential of bioactive compounds extracted from T. chuii using green biobased solvents (ethyl acetate, AcOEt, and cyclopentyl methyl ether, CPME) under pressurized liquid extraction (PLE) conditions and supercritical fluid extraction (SFE). Response surface optimization was used to study the effect of temperature and solvent composition on the neuroprotective properties of the PLE extracts, including anticholinergic activity, reactive oxygen/nitrogen species (ROS/RNS) scavenging capacity, and anti-inflammatory activity. Optimized extraction conditions of 40 °C and 34.9% AcOEt in CPME resulted in extracts with high anticholinergic and ROS/RNS scavenging capacity, while operation at 180 °C and 54.1% AcOEt in CPME yielded extracts with potent anti-inflammatory properties using only 20 min. Chemical characterization revealed the presence of carotenoids (neoxanthin, violaxanthin, zeaxanthin, α- and ß-carotene) known for their anti-cholinesterase, antioxidant, and anti-inflammatory potential. The extracts also exhibited high levels of omega-3 polyunsaturated fatty acids (PUFAs) with a favorable ω-3/ω-6 ratio (>7), contributing to their neuroprotective and anti-inflammatory effects. Furthermore, the extracts were found to be safe to use, as cytotoxicity assays showed no observed toxicity in HK-2 and THP-1 cell lines at or below a concentration of 40 µg mL-1. These results highlight the neuroprotective potential of Tetraselmis chuii extracts, making them valuable in the field of nutraceutical production and emphasize the interest of studying new green solvents as alternatives to conventional toxic solvents.

Sweet basil (Ocimum basilicum) leaf and seed extracts alleviate neuronal dysfunction in aluminum chloride-induced neurotoxicity in Drosophila melanogaster Meigen model.

Ocimum basilicum is an important medicinal plant and culinary herb generally known as sweet basil (SB). These plants are effective radical scavengers, that have been employed in treatment of nervous system disorders, and thus, could be beneficial for the management of neurodegenerative diseases (NDs). Current clinical treatments for NDs present several side effects, therefore, there is need to develop new treatments that can mitigate these deadly diseases. Hence, this study investigated the neuroprotective activities of SB leaf and seed in aluminum chloride (AlCl3)-induced toxicity in Drosophila melanogaster. HPLC characterization of the leaves and seeds were carried out. AlCl3-diet was used to induce neurodegeneration and treated flies received SB leaf and seed extracts-supplemented diet. Survival and locomotor performance activities/levels of oxidative biomarkers [reactive oxygen species (ROS), thiobarbituric acid reactive species (TBARS), total thiol, catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST)], enzymes linked with neurodegeneration (acetylcholinesterase (AChE) and monoamine oxidase (MAO)) were investigated. SB leaf had significantly (p < 0.05) higher polyphenol contents; gallic acid and P-coumaric acid were the most abundant polyphenol in the leaf and seed respectively. Percentage survival and locomotor rates, level/activities of total thiol, catalase, SOD and GST were significantly (p < 0.05) reduced while ROS, TBARS, AChE and MAO activities were significantly (p < 0.05) increased in AlCl3-diet-fed flies. Treatment with SB leaf and seed diet lessened these observed impairments. However, SB leaf had better neuroprotective activities that could be related to the observed higher phenolic constituents. Hence, SB leaf diet may offer improved therapeutic effect in NDs.

Buffalo colostrum peptide mitigates Parkinson's disease pathophysiology through Cullin-3 inhibition.

Colostrum/Milk is a chief repertoire of antioxidant peptides. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a viable target for Parkinson's Disease (PD), as this pathway deduced to be impaired in PD. Cullin-3 is one of the crucial E3 ligase responsible for its regulation. The present study screened peptide libraries of buffalo colostrum & milk peptides for Cullin-3 inhibition, thus ensuing activation of Nrf2 to alleviate the molecular etiopathology in PD using the C. elegans as a model. The structure was modelled, binding sites analyzed and peptide-interactions analyzed by docking. Among the 55 sequences (≤1 kDa), the peptide SFVSEVPEL having the highest dock score (-16.919) was synthesized and evaluated for its effects on oxidative stress markers, antioxidant enzymes, neurochemical marker and Nrf2/Skn-1 levels. The lead peptide alleviated the oxidative pathophysiology and behavioural deficits associated with PD in C. elegans.

Dihydropashanone Isolated from Lindera erythrocarpa, a Potential Natural Product for the Treatment of Neurodegenerative Diseases.

Lindera erythrocarpa, a flowering plant native to eastern Asia, has been reported to have neuroprotective activity. However, reports on the specific bioactive compounds in L. erythrocarpa are finite. The aim of this study was to investigate the anti-neuroinflammatory and neuroprotective effects of the compounds isolated from L. erythrocarpa. Dihydropashanone, a compound isolated from L. erythrocarpa extract, was found to have protected mouse hippocampus HT22 cells from glutamate-induced cell death. The antioxidant and anti-inflammatory properties of dihydropashanone in mouse microglial BV2 and HT22 cells were explored in this study. The results reveal that dihydropashanone inhibits lipopolysaccharide-induced inflammatory response and suppresses the activation of nuclear factor (NF)-κB in BV2 cells. In addition, dihydropashanone reduced the buildup of reactive oxygen species in HT22 cells and induced activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway in BV2 and HT22 cells. Our results suggest that dihydropashanone reduces neuroinflammation by decreasing NF-κB activation in microglia cells and protects neurons from oxidative stress via the activation of the Nrf2/HO-1 pathway. Thus, our data suggest that dihydropashanone offers a broad range of applications in the treatment of neurodegenerative illnesses.

Health-promoting compounds in Amomum villosum Lour and Amomum tsao-ko: Fruit essential oil exhibiting great potential for human health.

The Zingiberaceae family serves as a diverse repository of bioactive phytochemicals, comprising approximately 52 genera and 1300 species of aromatic perennial herbs distinguished by their distinct creeping horizontal or tuberous rhizomes. Amomum villosum Lour. and Amomum tsao-ko Crevost & Lemaire., are the important plants of family Zingiberaceae that have been widely used in traditional medicine for the treatment of many ailments. The Amomum species are employed for their aromatic qualities and are valued as spices and flavorings. In the essential oils (EOs) of Amomum species, notable constituents include, camphor, methyl chavicol, bornyl acetate, trans-p-(1-butenyl) anisole, α-pinene, and ß-pinene. OBJECTIVE: The aim of this review is to present an overview of pharmacological studies pertaining to the extracts and secondary metabolites isolated from both species. The foremost objective of review is not only to increase the popularity of Amomum as a healthy food choice but also to enhance its status as a staple ingredient for the foreseeable future. RESULT: We endeavored to gather the latest information on antioxidant, antidiabetic, anticancer, antiobesity, antimicrobial, and anti-inflammatory properties of plants as well as their role in neuroprotective diseases. Research conducted through in-vitro studies, animal model, and compounds analysis have revealed that both plants exhibit a diverse array health promoting properties. CONCLUSION: the comprehensive review paper provides valuable insights into the diverse range of bioactive phytochemicals found in A. villosum and A. tsao-ko, showcasing their potential in preventing diseases and promoting overall human well-being. The compilation of information on their various health-enhancing properties contributes to the broader understanding of these plants and their potential applications in traditional medicine and beyond.

Phyto-pharmacological Potential of Aegle marmelos (L.) for Neurological Disorders: Progress and Prospects.

BACKGROUND: Aegle marmelos, an Indian plant, has been extensively utilized by the people of the Indian subcontinent over about 5000 years. The leaves, bark, roots, and fruits, including seeds, are widely used to cure a variety of diseases in the Indian traditional system of medicine, Ayurveda, along with numerous folk medicines. By revealing the existence of significant bioactive chemicals, modern research has effectively substantiated the therapeutic effects of bael. OBJECTIVE: The objective of this study was to review the literature regarding A. marmelos geographical distribution, morphology, therapeutic benefits, and phytochemicals found in the bael leaves, fruits, and other parts of the plant that offer a wide range of pharmacological applications in neurological disorders. METHODOLOGY: A thorough literature search was conducted using five computerized databases, such as PubMed, Google Scholar, ScienceDirect, Elsevier, and Wiley Online Library (WOL), by using standard keywords "A. marmelos," "Geographical distribution," "Morphological description," "Ethnobotanical Uses," "Phytoconstituents" and "Neuroprotective activities" for review papers published between 1975 and 2023. A small number of earlier review articles focused on phyto-pharmacological potential of Aegle marmelos (L.) for neurological disorders. RESULTS: According to some research, Aegle marmelos extracts potentially have neuroprotective benefits. This is due to its capacity to alter cellular mechanisms that cause neuronal damage. CONCLUSION: Neurodegenerative illnesses usually induce permanent neuronal network loss overall the brain along with the spinal cord (CNS), resulting in chronic functional impairments. The review summarizes the multiple aspects and processes of A. marmelos extract and its components in several models of neurodegenerative diseases such as anxiety, epilepsy, depression, Parkinson's disease, Alzheimer's disease, and others. MDA, nitrite, TNF-, and IL-6 levels were dramatically elevated, whereas glutathione levels were significantly lowered in the hippocampus of STZ-treated rats. Furthermore, STZ-treated rats showed a substantial drop in catalase activity and an increase in AChE activity, indicating cholinergic hypofunction and neuronal injury. The neuroprotective ability of A. marmelos against STZ-induced oxidative stress and cognitive loss in rats suggests that it has therapeutic relevance in Alzheimer's disease (AD).

Investigating Bacopa monnieri L. Therapeutic Potential for the Treatment of Neurological Diseases.

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (Aß) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects.

Curcumin and omega-3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease.

Curcumin and omega-3 polyunsaturated fatty acids (ω-3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω-3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω-3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.

Exploring the therapeutic potential of quercetin: A focus on its sirtuin-mediated benefits.

As the global population ages, preventing lifestyle- and aging-related diseases is increasing, necessitating the search for safe and affordable therapeutic interventions. Among nutraceuticals, quercetin, a flavonoid ubiquitously present in various plants, has garnered considerable interest. This review aimed to collate and analyze existing literature on the therapeutic potentials of quercetin, especially its interactions with SIRTs and its clinical applicability based on its bioavailability and safety. This narrative review was based on a literature survey spanning from 2015 to 2023 using PUBMED. The keywords and MeSH terms used were: "quercetin" AND "bioavailability" OR "metabolism" OR "metabolites" as well as "quercetin" AND "SIRTuin" OR "SIRT*" AND "cellular effects" OR "pathway" OR "signaling" OR "neuroprotective" OR "cardioprotective" OR "nephroprotective" OR "antiatherosclerosis" OR "diabetes" OR "antidiabetic" OR "dyslipidemia" AND "mice" OR "rats". Quercetin demonstrates multiple therapeutic activities, including neuroprotective, cardioprotective, and anti-atherosclerotic effects. Its antioxidant, anti-inflammatory, antiviral, and immunomodulatory properties are well-established. At a molecular level, it majorly interacts with SIRTs, particularly SIRT1 and SIRT6, and modulates numerous signaling pathways, contributing to its therapeutic effects. These pathways play roles in reducing oxidative stress, inflammation, autophagy regulation, mitochondrial biogenesis, glucose utilization, fatty acid oxidation, and genome stability. However, clinical trials on quercetin's effectiveness in humans are scarce. Quercetin exhibits a wide range of SIRT-mediated therapeutic effects. Despite the compelling preclinical data, more standardized clinical trials are needed to fully understand its therapeutic potential. Future research should focus on addressing its bioavailability and safety concerns.

Role of Network Pharmacology in Prediction of Mechanism of Neuroprotective Compounds.

Network pharmacology is an emerging pioneering approach in the drug discovery process, which is used to predict the therapeutic mechanism of compounds using various bioinformatic tools and databases. Emerging studies have indicated the use of network pharmacological approaches in various research fields, particularly in the identification of possible mechanisms of herbal compounds/ayurvedic formulations in the management of various diseases. These techniques could also play an important role in the prediction of the possible mechanisms of neuroprotective compounds. The first part of the chapter includes an introduction on neuroprotective compounds based on literature. Further, network pharmacological approaches are briefly discussed. The use of network pharmacology in the prediction of the neuroprotective mechanism of compounds is discussed in detail with suitable examples. Finally, the chapter concludes with the current challenges and future prospectives.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Two new quinoline alkaloid with neuroprotective activities from Xylaria longipes.

Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.

Protective effect of Danshensu against neurotoxicity induced by monosodium glutamate in adult mice and their offspring.

Excessive neuronal excitation by glutamate is a well-established cause of neurotoxicity, leading to severe impairment of brain function. Excitotoxicity is a key factor in numerous neurodegenerative conditions. In this study, we investigated the neuroprotective effects of Danshensu (DSS) against monosodium glutamate (MSG)-induced neurotoxicity in adult mice and their offspring. We randomly divided one hundred 8-week-old Kunming mice (equal number of males and females) into a control group and an experimental group. The experimental group was further subdivided into various treatment groups, including MSG gavage treatment, bwbw DSS treatment group 1 (bwbw DSS treatment group 2, a drug control group, and a normal control group (receiving an equal volume of physiological saline for ten consecutive days). Additionally, another one hundred healthy 8-week-old Kunming mice were similarly divided into groups and treated. These mice were paired randomly (one male and one female) and pregnant females were housed separately to obtain offspring. Subsequently, we conducted histological and behavioral analyses on adult mice and their offspring. MSG treatment induced significant cellular edema and hippocampal damage in both the treated mice and their offspring. However, varying doses of DSS effectively counteracted the neurotoxic effects of MSG, with no adverse impact on brain tissue structure or neural function in either adult mice or their offspring. Behavioral experiments further confirmed that DSS exerted a substantial protective effect against MSG-induced impairment of learning and memory in the treated adult mice and their offspring, in addition to mitigating central nervous system overexcitation and inhibiting exploratory behavior. In conclusion, DSS exerts significant protective effects against MSG-induced neurotoxicity in both adult mice and their offspring.

Gardenia yellow pigment: Extraction methods, biological activities, current trends, and future prospects.

Food coloring plays a vital role in influencing consumers' food choices, imparting vibrant and appealing colors to various food and beverage products. Synthetic food colorants have been the most commonly used coloring agents in the food industry. However, concerns about potential health issues related to synthetic colorants, coupled with increasing consumer demands for food safety and health, have led food manufacturers to explore natural alternatives. Natural pigments not only offer a wide range of colors to food products but also exhibit beneficial bioactive properties. Gardenia yellow pigment is a water-soluble natural pigment with various biological activities, widely present in gardenia fruits. Therefore, this paper aims to delve into Gardenia Yellow Pigment, highlighting its significance as a food colorant. Firstly, a thorough understanding and exploration of various methods for obtaining gardenia yellow pigment. Subsequently, the potential functionality of gardenia yellow pigment was elaborated, especially its excellent antioxidant and neuroprotective properties. Finally, the widespread application trend of gardenia yellow pigment in the food industry was explored, as well as the challenges faced by the future development of gardenia yellow pigment in the field of food and health. Some feasible solutions were proposed, providing valuable references and insights for researchers, food industry professionals, and policy makers.

Jiawei Kongsheng Zhenzhong Pill: marker compounds, absorption into the serum (rat), and Q-markers identified by UPLC-Q-TOF-MS/MS.

Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.

Neuroprotective effects of Shenghui decoction via inhibition of the JNK/p38 MAPK signaling pathway in an AlCl3-induced zebrafish (Danio rerio) model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multi-factorial degenerative disease, and multi-targeted therapies targeting multiple pathogenic mechanisms should be explored. Shenghui decoction (SHD) is an ancient traditional Chinese medicine (TCM) formula used clinically to alleviate AD. However, the precise mechanism of action of SHD as a therapeutic agent for AD remains unclear. AIM OF THE STUDY: This study investigated the neuroprotective properties and potential mechanisms of action of SHD in mitigating AD-like symptoms induced by AlCl3 in a zebrafish model. MATERIALS AND METHODS: Active components of SHD were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Zebrafish were exposed to AlCl3 (200 µg/L) for 30 days to establish an AD zebrafish model. AlCl3-exposed zebrafish were treated with SHD or donepezil. Behavioral tests were used to assess learning and memory, locomotor activity, and AD-related anxiety and aggression in AlCl3-exposed zebrafish. Nissl staining and transmission electron microscopy were used to evaluate histological alterations in brain neurons. The concentrations of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-1ß, IL-1ß) were quantified using Enzyme-linked immunosorbent assay (ELISA). Markers of oxidative stress and cholinergic activity (acetylcholinesterase, AChE) were detected using biochemical assays. Western blotting and immunofluorescence were used to detect the protein expression levels of Aß, p-tau, PSD-95, synaptophysin, TLR4, phosphorylation of NF-κB p65, p38, and JNK. RESULTS: Fifteen SHD compounds were identified by UPLC-MS/MS analysis. SHD improved AlCl3-induced dyskinesia, learning and memory impairment, anxiety-like behavior, and aggressive behavior in zebrafish. AlCl3-exposed zebrafish showed AD-like pathology, overexpression of Aß, hyperphosphorylated tau protein, marked neuronal damage, decreased expression of synaptic proteins, synaptophysin, and PSD-95, and impairment of synaptic structural plasticity. These effects were reversed by the SHD treatment. We also observed that SHD ameliorated oxidative stress and decreased AChE activity and inflammatory cytokine levels. These effects are similar to those observed for donepezil. Meanwhile, SHD could decrease the protein expression of TLR4 and inhibit phosphorylation of NF-κB, JNK, and p38 MAPK. These results demonstrate that SHD has the potential to exert neuroprotective effects, which may be partly mediated via inhibition of the JNK/p38 MAPK signaling pathway. CONCLUSIONS: Our findings revealed the therapeutic mechanism of SHD in mitigating AD progression and suggested that SHD is a potent neuroprotectant that contributes to the future development of TCM modernization and broader clinical applications.

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray.

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.

Abietane diterpenoids with anti-neuroinflammation activity from Rosmarinus officinalis.

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1-6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α,ß-unsaturated five-element ketone. All the compounds and four compounds (13-16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5, 8, 9, 11, and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 µM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation.