Computational Docking as a Tool in Guiding the Drug Design of Rutaecarpine Derivatives as Potential SARS-CoV-2 Inhibitors.

COVID-19 continues to spread around the world. This is mainly because new variants of the SARS-CoV-2 virus emerge due to genomic mutations, evade the immune system and result in the effectiveness of current therapeutics being reduced. We previously established a series of detection platforms, comprising computational docking analysis, S-protein-based ELISA, pseudovirus entry, and 3CL protease activity assays, which allow us to screen a large library of phytochemicals from natural products and to determine their potential in blocking the entry of SARS-CoV-2. In this new screen, rutaecarpine (an alkaloid from Evodia rutaecarpa) was identified as exhibiting anti-SARS-CoV-2 activity. Therefore, we conducted multiple rounds of structure-activity-relationship (SAR) studies around this phytochemical and generated several rutaecarpine analogs that were subjected to in vitro evaluations. Among these derivatives, RU-75 and RU-184 displayed remarkable inhibitory activity when tested in the 3CL protease assay, S-protein-based ELISA, and pseudovirus entry assay (for both wild-type and omicron variants), and they attenuated the inflammatory response induced by SARS-CoV-2. Interestingly, RU-75 and RU-184 both appeared to be more potent than rutaecarpine itself, and this suggests that they might be considered as lead candidates for future pharmacological elaboration.

Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Synergy of botanical drug extracts from Dracaena cochinchinensis stemwood and Ardisia elliptica fruit in multifunctional effects on neuroprotection and anti-inflammation.

Combination therapy is one of the promising approaches in developing therapeutics to cure complex diseases, such as Alzheimer's disease (AD). In Thai traditional medicines, the clinical application often comprises multiple botanical drugs as a formulation. The synergistic interactions between botanical drugs in combination therapies are proposed to have several advantages, including increased therapeutic efficacy, and decreased toxicity and/or adverse effects. This study aimed to explore the therapeutic functions of a botanical hybrid preparation (BHP) of two botanical drugs within a traditional multi-herbal formulation. The synergistic actions of BHP of Dracaena cochinchinensis stemwood (DCS) and Ardisia elliptica fruit (AEF) at a specific ratio of 1:9 w/w were illustrated in neuroprotection and anti-inflammation. In cultured PC12 cells, BHP of DCS and AEF showed synergistic functions in inducing neuronal differentiation, characterized by neurofilament expression and neurite outgrowth. In addition, BHP of DCS and AEF exhibited a synergistic effect in inhibiting the aggregation of Aß, a hallmark of AD pathology. The activated BV2 microglial cells induced by LPS were synergistically suppressed by the BHP of DCS and AEF, as evaluated by the expression of pro-inflammatory markers, including TNF-α, IL-1ß, and iNOS, as well as the morphological change of microglial cells. The findings suggested that the effects of BHP of DCS and AEF were greater than individual botanical drugs in a specific ratio of 1:9 w/w to enhance neuroprotective and anti-inflammatory functions.

Nepetin Attenuates Atopic Dermatitis in HaCaT Cells and BALB/c Mice Through MyD88-MKK3/6-Akt Signaling.

Nepetin is a type of O-methylated flavone (6-hydroxy luteolin) and has been found in many herbal medicines that exhibit various pharmacological properties, including anti-inflammatory responses. Here, we aimed to investigate the efficacy of nepetin in attenuating inflammatory responses in cultured keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in BALB/c mice. Various assay methods including cell viability, flow cytometry, fluorometry, confocal microscopy, western blot, ELISA techniques, staining methods, score and scratch frequency assessment, etc. were employed to explore the mechanisms. LPS-treated keratinocytes showed a significant increase in inflammatory mediators (iNOS, COX-2, PGES2, and NO) and cytokines (IL-1ß, IL-6, and TNF-α) in a dose-dependent manner. Treatment with nepetin prevented LPS-induced cell death and inhibited inflammatory mediators and the production of cytokines in cultured keratinocytes. This inhibition was achieved by nepetin, which inhibited LPS-induced ROS production and the translocation of NF-κB in the cultures, thereby inhibiting the generation of inflammatory mediators and/or cytokines. In a mouse model of AD, treatment with nepetin reduced skin inflammation symptoms in a dose-dependent manner, as evidenced by the significant reduction of inflammation- related cytokines, skin lesions, and behavior scores. Based on the present in vitro and in vivo study, nepetin is the safest bioactive compound with potential therapeutic applications for AD-related skin lesions and adverse skin reactions.

Comparative proteomic analysis of edible bird's nest from different origins.

Edible bird's nest (EBN) mainly made of saliva that secreted by a variety of swiftlets is a kind of precious traditional Chinese medicine. EBNs from different biological and geographical origins exhibit varieties in morphology, material composition, nutritive value and commercial value. Here, we collected four different EBN samples from Huaiji, China (Grass EBN), Nha Trang, Vietnam (Imperial EBN) and East Kalimantan, Indonesia (White EBN and Feather EBN) respectively, and applied label-free quantitative MS-based proteomics technique to identify its protein composition. First, phylogenetic analysis was performed based on cytb gene to identify its biological origin. Second, a total of 37 proteins of EBNs were identified, among which there were six common proteins that detected in all samples and exhibited relatively higher content. Gene ontology analysis revealed the possible function of EBN proteins, and principal component analysis and hierarchical clustering analysis based on 37 proteins were performed to compare the difference of various EBNs. In summary, our study deciphered the common and characteristic protein components of EBNs of different origins and described their possible functions by GO enrichment analysis, which helps to establish an objective and reliable quality evaluation system.

Flavonoids from Seabuckthorn (Hippophae rhamnoides L.) restore CUMS-induced depressive disorder and regulate the gut microbiota in mice.

Seabuckthorn (Hippophae rhamnoides L.), which is enriched with flavonoids, including isorhamnetin, quercetin and kaempferol, is a representative example of "medicine food homology" targeting several diseases. Major depressive disorders seriously threaten mental health worldwide and may even lead to death. Chronic unpredictable mild stress (CUMS)-induced depressive-like symptoms in mice are usually considered as the highest similarity to the situation in humans. Herein, we determined the potential functions of the flavonoid-enriched fraction from Seabuckthorn, which was named SBF, in treating major depressive disorder in mice. In the CUMS-induced mouse model, the intake of SBF reversed their depressive behaviors and relieved the CUMS-disturbed levels of neurotrophins, neurotransmitters, stress-related hormones, and inflammation-related cytokines. Additionally, the treatment of depressive mice with SBF showed ability to regulate the gut microbiota, especially in decreasing the abundance of Lactobacillaceae, while increasing the abundance of Lachnospiraceae at the family level. The results suggest the beneficial effects of Seabuckthorn flavonoids in functioning as a health food supplement to treat major depressive disorders.

The flavonoids induce the transcription of mRNA encoding erythropoietin in cultured embryonic stem cells via the accumulation of hypoxia-inducible factor-1α.

Flavonoids are the most common phytochemicals in vegetables and herbal products. The beneficial functions of flavonoids in the brain and erythropoietic system have been proposed. Erythropoietin (EPO) is a potent protective agent in the brain; but which has difficulty to cross the blood brain barrier (BBB). Here, about 60 flavonoids were screened for their potential activation on the transcription of EPO mRNA in the neuronal embryonic stem cell lines, NT2/D1 and PC12. Amongst the screened flavonoids, formononetin, calycosin, ononin, chrysin, baicalein and apigenin showed robust up regulation of EPO production via enhancement of hypoxia response element (HRE) activity in cultured embryonic stem cells. In addition, the flavonoids showed activation of HRE activity by having increased accumulation of HIF-1α, but not on level of HIF-1ß, in the cultures. The accumulation of HIF-1α was attributed to up regulation of HIF-1α mRNA and blockade of HIF-1α degradation upon treatment of the flavonoids. These results suggested a promising trend of developing commercial products of flavonoids as food supplements tailored for brain health.

The extracts of Dracaena cochinchinensis stemwood suppress inflammatory response and phagocytosis in lipopolysaccharide-activated microglial cells.

BACKGROUND: Neuroinflammation is a pivotal process in the brain that contributes to the development of neurodegenerative diseases, such as Alzheimer's disease (AD). During neuroinflammation, the over-activation of microglial cells can drive the pathological processes underlying AD, including an increase in amyloid ß (Aß) production and accumulation, ultimately leading to neuronal and synaptic loss. Dracaena cochinchinensis (Lour.) S.C. Chen, also known as "Chan-daeng" in Thai, belongs to the Asparagaceae family. In Thai traditional medicine, it has been used as an antipyretic, pain reliever, and anti-inflammatory agent. However, the effects of D. cochinchinensis on neuroinflammation are yet to be determined. PURPOSE: We aimed to evaluate the anti-neuroinflammatory activities of D. cochinchinensis stemwood extract in activated microglia. METHODS: In this study, lipopolysaccharide (LPS), a potent pro-inflammatory stimulus, was used to activate microglial BV2 cells, as a cell model of neuroinflammation. Our investigation included several techniques, including qRT-PCR, ELISA, Western blotting, phagocytosis, and immunofluorescence staining, to examine the potential anti-inflammatory effects of D. cochinchinensis stemwood. RESULTS: D. cochinchinensis stemwood, named DCS, was extracted with ethanol and water. The extracts of DCS showed dose-dependent anti-inflammatory effects, markedly suppressing the LPS-mediated mRNA expression of pro-inflammatory factors, including IL-1ß, TNF-α, and iNOS, while increasing expression of the anti-inflammatory biomarker Arg1 in both BV2 microglia and RAW264.7 macrophages. DCS extracts also decreased the protein levels of IL-1ß, TNF-α, and iNOS. These findings were correlated with the suppression of phosphorylated proteins of p38, JNK, and Akt in the LPS-activated microglia. Moreover, DCS extracts significantly attenuated excessive phagocytosis of beads and Aß fibrils during the LPS-mediated microglial activation. CONCLUSION: Taken together, our results indicated that DCS extracts had anti-neuroinflammatory properties by suppressing the expression of pro-inflammatory factors, increasing the expression of the anti-inflammatory biomarker Arg1, and modulating excessive phagocytosis in activated microglia. These findings suggested that DCS extract could be a promising natural product for the treatment of neuroinflammatory and neurodegenerative diseases, like AD.

The neurotrophic activities of brain-derived neurotrophic factor are potentiated by binding with apigenin, a common flavone in vegetables, in stimulating the receptor signaling.

AIMS: We aimed to identify the neurotrophic activities of apigenin (4',5,7-trihydroxyflavone) via its coordination with brain-derived neurotrophic factor (BNDF) and an elevated signaling of tyrosine kinase receptor B (Trk B receptor). METHODS: The direct binding of apigenin to BDNF was validated by ultrafiltration and biacore assay. Neurogenesis, triggered by apigenin and/or BDNF, was determined in cultured SH-SY5Y cells and rat cortical neurons. The amyloid-beta (Aß)25-35 -induced cellular stress was revealed by propidium iodide staining, mitochondrial membrane potential, bioenergetic analysis, and formation of reactive oxygen species levels. Activation of Trk B signaling was tested by western blotting. RESULTS: Apigenin and BDNF synergistically maintained the cell viability and promoted neurite outgrowth of cultured neurons. In addition, the BDNF-induced neurogenesis of cultured neurons was markedly potentiated by applied apigenin, including the induced expressions of neurofilaments, PSD-95 and synaptotagmin. Moreover, the synergy of apigenin and BDNF alleviated the (Aß)25-35 -induced cytotoxicity and mitochondrial dysfunction. The synergy could be accounted by phosphorylation of Trk B receptor, and which was fully blocked by a Trk inhibitor K252a. CONCLUSION: Apigenin potentiates the neurotrophic activities of BDNF through direct binding, which may serve as a possible treatment for its curative efficiency in neurodegenerative diseases and depression.

Flavonoids from Seabuckthorn (Hippophae rhamnoides L.) mimic neurotrophic functions in inducing neurite outgrowth in cultured neurons: Signaling via PI3K/Akt and ERK pathways.

BACKGROUND: Various brain disorders, including neurodegenerative diseases and major depressive disorders, threaten an increasing number of patients. Seabuckthorn, a fruit from Hippophae rhamnoides L., is an example of "medicine food homology". The fruit has enriched flavonoids that reported to have benefits in treating cognitive disorders. However, the studies on potential functions of Seabuckthorn and/or its flavonoid-enriched fraction in treating neurodegenerative disorders are limited. PURPOSE: This study aimed to determine the ability and mechanism of the flavonoid-enriched fraction of Seabuckthorn (named as SBF) in mimicking the neurotrophic functions in inducing neurite outgrowth of cultured neurons. METHODS: Cultured PC12 cell line, SH-SY5Y cell line and primary neurons (cortical and hippocampal neurons isolated from E17-19 SD rat embryos) were the employed models to evaluate SBF in inducing neurite outgrowth by comparing to the effects of NGF and BDNF. Immuno-fluorescence staining was applied to identify the morphological change during the neuronal differentiation. Luciferase assay was utilized for analyzing the transcriptional regulation of neurofilaments and cAMP/CREB-mediated gene. Western blot assay was conducted to demonstrate the expressions of neurofilaments and phosphorylated proteins. RESULTS: The application of SBF induced neuronal cell differentiation, and this differentiating activation was blocked by the inhibitors of PI3K/Akt and ERK pathways. Additionally, SBF showed synergy with neurotrophic factors in stimulating the neurite outgrowth of cultured neurons. Moreover, the major flavonoids within SBF, i.e., isorhamnetin, quercetin and kaempferol, could account for the neurotrophic activities of SBF. CONCLUSION: Seabuckthorn flavonoids mimicked neurotrophic functions in inducing neuronal cell differentiation via activating PI3K/Akt and ERK pathways. The results suggest the beneficial functions of Seabuckthorn as a potential health food supplement in treating various brain disorders, e.g., neurodegenerative diseases.

The ethanolic extract of peanut shell attenuates the depressive-like behaviors of mice through modulation of inflammation and gut microbiota.

Peanut shell is an agricultural byproduct being wasted on a large scale, which is in urgent need to be recycled. To fully utilize its pharmacological ingredients, e.g. luteolin, eriodyctiol, and 5,7-dihydroxychromone, we evaluated the curative effect of ethanol extract deriving from peanut shell (PSE) in treating chronic unpredictable mild stress (CUMS)-induced depressive mice. The chronic stress lasted for 10 weeks, and PSE at 100-900 mg/kg/day was gavaged to mice in the last 2 weeks of modeling. The depressive behaviors were assessed by analyses of sucrose preference, tail suspension, and forced swimming. The brain injury was demonstrated by Hematoxylin and Eosin (H&E), Nissl body, and TdT-mediated dUTP nick end labeling (TUNEL) stainings in the mouse hippocampus. Biochemical indicators were analyzed, including levels of neurotrophic factors, neurotransmitters, stress hormones, and inflammatory mediators. The feces were collected for the 16S rDNA sequencing of gut microbiome. Administration of PSE improved the sucrose water consumption of depressive mice, while it decreased the immobile time in tail suspension and forced swimming tests. Meanwhile, the anti-depressive effect of PSE was supported by ameliorated histochemical staining, increased levels of neurotrophic factors and neurotransmitters, as well as down-regulated stress hormones. Furthermore, the treatment of PSE was able to mitigate the levels of inflammatory cytokines in brain, serum, and small intestine. Besides, the tight junction proteins, e.g., occludin and ZO-1, of gut showed elevated expressions, which coincided with the elevated abundance and diversity of gut microbiota upon PSE treatment. This study validated the therapeutic efficacy of PSE in fighting against depression, as well as its modulatory action on inflammation and gut microbiota, which promoted the recycling of this agricultural waste to be health supplements of added value.

The Ethanol Extract of Evodiae Fructus and Its Ingredient, Rutaecarpine, Inhibit Infection of SARS-CoV-2 and Inflammatory Responses.

COVID-19, derived from SARS-CoV-2, has resulted in millions of deaths and caused unprecedented socioeconomic damage since its outbreak in 2019. Although the vaccines developed against SARS-CoV-2 provide some protection, they have unexpected side effects in some people. Furthermore, new viral mutations reduce the effectiveness of the current vaccines. Thus, there is still an urgent need to develop potent non-vaccine therapeutics against this infectious disease. We recently established a series of detecting platforms to screen a large library of Chinese medicinal herbs and phytochemicals. Here, we reveal that the ethanolic extract of Evodiae Fructus and one of its components, rutaecarpine, showed promising potency in inhibiting the activity of 3C-like (3CL) protease, blocking the entry of the pseudo-typed SARS-CoV-2 (including wild-type and omicron) into cultured cells. In addition, inflammatory responses induced by pseudo-typed SARS-CoV-2 were markedly reduced by Evodiae Fructus extract and rutaecarpine. Together our data indicate that the herbal extract of Evodiae Fructus and rutaecarpine are potent anti-SARS-CoV-2 agents, which might be considered as a treatment against COVID-19 in clinical applications.

Novel phenylpropanoids and isoflavone glycoside are isolated and identified from the carob pods (Ceratonia siliqua L.).

Two new phenylpropanoids (1 and 2) and one new isoflavone glycoside (3), along with nine known compounds (4 - 12), were isolated from the pod of Ceratonia siliqua L. Their chemical structures were elucidated based on extensive spectroscopic analyses (1 D and 2 D NMR, UV, IR, and HRESIMS) and compared with the literature data. In addition, all isolated compounds were evaluated in vitro for inhibitory activity against acetylcholinesterase (AChE). Compounds 4, 5, and 12 showed inhibitory activity against acetylcholinesterase (AChE) with IC50 values ranging from 15.0 to 50.2 µM.

The UV-induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor-mediated phagocytosis.

The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as 'skin synapse'. Here, the role of cholinergic molecules, i.e. ACh and α7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV-induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor or an α7 nAChR agonist. By contrast, the antagonist of α7 nAChR was able to fully block the UV-induced phagocytosis, suggesting the role of α7 nAChR in this event. The intracellular Ca++ mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV-mediated Ca++ mobilization, triggered by BAPTA-AM or α7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA-AM or α7 nAChR antagonist. The result suggests that the cholinergic system, especially α7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.

Edible bird's nest, an Asian health food supplement, possesses anti-inflammatory responses in restoring the symptoms of atopic dermatitis: An analysis of signaling cascades.

Edible bird's nest (EBN) is a Chinese delicacy possessing skin rejuvenating functions. To verify skin anti-inflammatory function of EBN, water extract and enzymatic digest of EBN, as well as the major sialic acid, N-acetyl neuraminic acid (NANA), were probed in TNF-α-treated HaCaT keratinocytes. The mRNA expressions of pro-inflammatory cytokines, e.g., IL-1ß, IL-6, TNF-α, and an enzyme responsible for inflammatory response, i.e., Cox-2, as well as filaggrin and filaggrin-2, were markedly altered after treating with different preparations of EBN. The EBN-mediated responses could be accounted by its robust reduction of reactive oxygen species (ROS), NF-κB signaling and phosphorylation of p38 MAPK and JNK, as triggered by TNF-α-induced inflammation. The anti-inflammatory response of EBN was further supported in animal model. In 2,4-dinitrochlorobenzene (DNCB)-induced dermatitic mice, the effects on skin thickness, severity level of damage and scratching behavior, exerted by DNCB, were reversed after EBN treatments, in dose-dependent manners. In parallel, the levels of immune cells and pro-inflammatory cytokines in dermatitic skin were markedly reduced by treatment of EBN preparations. In general, NANA and enzymatic digest of EBN showed better anti-inflammatory responses in both models of in vitro and in vivo. These lines of evidence therefore suggest the possible application of EBN in treating atopic dermatitis.

Dracaena cochinchinensis stemwood extracts inhibit amyloid-ß fibril formation and promote neuronal cell differentiation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid plaques in the brain. The prevention of amyloid-ß (Aß)-induced neuronal toxicity is considered a major target for drug development for AD treatment. Dracaena cochinchinensis (Lour.) S.C. Chen, a Thai folk medicine named "Chan-Daeng," is a member of the Asparagaceae family. The stemwood of D. cochinchinensis has been traditionally used for its antipyretic, pain relief, and anti-inflammatory effects. The aim of the present study was to determine the pharmacological activities of ethanol and water extracts of D. cochinchinensis stemwood in blocking the Aß fibril formation, preventing Aß-mediated cell toxicity, and promoting neuronal differentiation in cultured PC12 cells. The herbal extracts of D. cochinchinensis stemwood prevented the formation of Aß fibrils and disassembled the aggregated Aß in a dose-dependent manner. Additionally, they prevented Aß fibril-mediated cell death. The synergy of the herbal extract with a low dose of the nerve growth factor showed an increase in the protein expression of neurofilaments, that is, NF68, NF160, and NF200. These findings suggest that the extracts of D. cochinchinensis stemwood may be used for AD treatment by targeting Aß fibril formation and inducing neuron regeneration.

The inclusion of extract from aerial part of Scutellaria baicalensis in feeding of pearl gentian grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceo-latus♂) promotes growth and immunity.

The root of Scutellaria baicalensis (Scutellaria Radix) has been used as herbal medicine for years in China; however, its stem and leaf (aerial part) are considered as waste. The water extract of aerial part of S. baicalensis, named as SBA, having anti-microbial property has been applied in fish aquaculture. To extend the usage of SBA in fish feeding, SBA was employed to feed pearl gentian grouper (a hybrid of Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂), and subsequently the total fish output, the levels of digestive enzymes and inflammatory cytokines were determined. Feeding the fish with different doses of SBA for two months, the body length and weight were significantly increased by 5%-10%. In parallel, the expressions of alkaline phosphatase and growth-related factors in bone, liver and muscle of SBA-fed fish were doubled, which could account the growth promoting effect of SBA. Besides, the activity of digestive enzyme, lipase, and the expressions of anti-inflammatory cytokines were markedly stimulated by 2-3 times under the feeding of 3% SBA-containing diet. The results indicated the growth promoting activity of SBA in culture of pearl gentian grouper, as well as the effect of SBA in strengthening the immunity. These beneficial effects of SBA feeding can increase the total yield of pearl gentian grouper in aquaculture. Thus, the re-cycle of waste products during the farming of S. baicalensis herb in serving as fish feeding should be encouraged.

The Extracts of Polygonum cuspidatum Root and Rhizome Block the Entry of SARS-CoV-2 Wild-Type and Omicron Pseudotyped Viruses via Inhibition of the S-Protein and 3CL Protease.

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.

A Herbal Mixture of Sesami Semen Nigrum and Longan Arillus Induces Neurite Outgrowth in Cultured Neurons and Shows Anti-Depression in Chronic Mild Stress-Induced Rats.

Medicinal food homology is referring to a group of food itself being considered as herbal medicine without a boundary of usage. Under the guidance of this food/medicine principle, the current study aims to develop anti-depressant from this food/medicine catalog. The herbal mixture of Sesami Semen Nigrum and Longan Arillus was evaluated in cultured PC12 rat pheochromocytoma cells, rat primary cortical neurons, and in chronic mild stress (CMS)-induced depressive rat model. The combination of two ethanolic extracts of Sesami Semen Nigrum and Longan Arillus in 1 : 1 ratio mimicked the function of nerve growth factor (NGF) and synergistically induced neurite outgrowth of PC12 cells. Besides, the expression and phosphorylation of tropomyosin receptor kinase A (TrkA) of the cultured cells were also elevated. This neurotrophic activity of herbal mixture was further supported by the increased expressions of biomarkers for neurogenesis and synaptogenesis in cortical neurons. Moreover, the depressed rats were soothed by the intake of herbal mixture, showing improved performance in behavior tests, as well as reversed levels of neurotransmitters and neurotrophic factors. Our results provide a new way to make full use of the current food/medicine resources, as to accelerate the development of therapeutics for depression.

Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.