Search

Laminaria japonica (LJ) is a common seaweed, which has been widely used as functional food and medicine, but its pharmaceutical activities in angiogenic regulation are unclear. Here, different lines of studies provide evidence to the suppressive effects of LJ extract in VEGF-medicated angiogenic function. In cellular level, LJ extract significantly inhibited VEGF-mediated endothelial cell proliferation, migration, invasion and tube formation. For in vivo verification, LJ extract suppressed the VEGF-induced formation of sub-intestinal vessels in zebrafish embryo model. In signalling cascades, LJ extract decreased the amount of phosphorylated VEGF receptor-2, as triggered by VEGF, and subsequently some key related downstream elements were obviously inactivated. In parallel, NO production and ROS formation, as induced by VEGF, were significantly attenuated. Thus, these preclinical findings promoted the possible development of LJ extract as a potential therapeutic agent for prevention and clinical treatment of angiogenesis-related diseases. © 2024 The Authors

Introduction: COVID-19, caused by the novel coronavirus SARS-CoV-2, has been a constant threat to public health since its outbreak in early 2019. Despite the development of vaccines and therapeutic drugs, the effectiveness of preventing both the infection and recurrence of this respiratory disease is limited due to emerging variants and their side effects. Hence, the development of potent and safe anti-SARS-CoV-2 therapeutic agents is still in urgent demand. Methods: We previously developed a screening platform comprising various pseudovirus entry tests in conjunction with a computational docking modulation protocol. With this platform, we demonstrated that the extract of Evodia Fructus and its main chemical component, rutaecarpine, inhibited SARS-CoV-2 entry by suppressing the S-protein-ACE2 complex. Results: Here, we reveal that when the extract of Stephaniae Tetrandrae Radix or its chemical component, tetrandrine (a well-known TPC2 inhibitor), is combined with Evodiae Fructus extract or rutaecarpine, respectively, then these act in a synergistic manner to block the entry of SARS-CoV-2. Conclusion: Given the fact that herbal extracts have been effectively used in clinical applications and have well-established safety records, our current findings suggest that these drug combinations might be considered as potential anti-COVID-19 treatments.

Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism in relieving the clinical symptoms is unclear. Several lines of evidence point to a strong link between constipation and gut microbiota. Short-chain fatty acids (SCFAs) and microbial metabolites have been shown to affect 5-HT synthesis by activating the GPR43 receptor localized on intestinal enterochromaffin cells, since 5-HT receptors are known to influence colonic peristalsis. The objective of this study was to evaluate the efficacy of XCQ in alleviating clinical symptoms in a mouse model of STC induced by loperamide. The application of loperamide leads to a decrease in intestinal transport and fecal water, which is used to establish the animal model of STC. In addition, the relationship between constipation and gut microbiota was determined. The herbal materials, composed of Rhei Radix et Rhizoma (Rhizomes of Rheum palmatum L., Polygonaceae) 55.2 g, Magnoliae Officinalis Cortex (Barks of Magnolia officinalis Rehd. et Wils, Magnoliaceae) 27.6 g, and Aurantii Fructus Immaturus (Fruitlet of Citrus aurantium L., Rutaceae) 36.0 g, were extracted with water to prepare the XCQ decoction. The constipated mice were induced with loperamide (10 mg/kg/day), and then treated with an oral dose of XCQ herbal extract (2.0, 4.0, and 8.0 g/kg/day) two times a day. Mosapride was administered as a positive drug. In loperamide-induced STC mice, the therapeutic parameters of XCQ-treated mice were determined, i.e., (i) symptoms of constipation, composition of gut microbiota, and amount of short-chain fatty acids in feces; (ii) plasma level of 5-HT; and (iii) expressions of the GPR43 and 5-HT4 receptor in colon. XCQ ameliorated the constipation symptoms of loperamide-induced STC mice. In gut microbiota, the treatment of XCQ in STC mice increased the relative abundances of Lactobacillus, Prevotellaceae_UCG_001, Prevotellace

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

Understanding the adaptive ecological divergence provides important information for revealing biodiversity generation and maintenance. Adaptive ecology divergence in populations occurs in various environments and locations, but its genetic underpinnings remain elusive. We generated a chromosome-level genome of Eleutheronema tetradactylum (~582 Mb) and re-sequenced 50 allopatric E. tetradactylum in two independent environmental axes in China and Thailand Coastal waters as well as 11 cultured relatives. A low level of whole genome-wide diversity explained their decreased adaptive potential in the wild environment. Demographic analysis showed evidence of historically high abundance followed by a continuous distinct decline, plus signs of recent inbreeding and accumulation of deleterious mutations. Extensive signals of selective sweeps with signs of local adaptation to environmental differentiation between China and Thailand at genes related to thermal and salinity adaptation were discovered, which might be the driving factors of the geographical divergence of E. tetradactylum. Many genes and pathways subjected to strong selection under artificial breeding were associated with fatty acids and immunity (ELOVL6L, MAPK, p53/NF-kB), likely contributing to the eventual adaptation of artificial selective breeding. Our comprehensive study provided crucial genetic information for E. tetradactylum, with implications for the further conservation efforts of this threatened and ecologically valuable fish.

Aflatoxin B1 (AFB1), a potent food-borne hepatocarcinogen, is the most toxic aflatoxin that induces liver injury in humans and animals. Species-specific sensitivities of aflatoxins cannot be fully explained by differences in the metabolism of AFB1 between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB1-induced liver injury. Here, mice were gavaged with AFB1 for 28 days. Then, the modulation of gut microbiota, colonic barrier, and liver pyroptosis and inflammation were analyzed. To further verify the direct role of gut microbiota in AFB1-induced liver injury, mice were treated with antibiotic mixtures (ABXs) to deplete the microbiota, and fecal microbiota transplantation (FMT) was conducted. The treatment of AFB1 in mice altered gut microbiota composition, such as increasing the relative abundance of Bacteroides, Parabacteroides, and Lactobacillus, inducing colonic barrier dysfunction and promoting liver pyroptosis. In ABX-treated mice, AFB1 had little effect on the colonic barrier and liver pyroptosis. Notably, after FMT, in which the mice were colonized with gut microbiota from AFB1-treated mice, colonic barrier dysfunction, and liver pyroptosis and inflammation were obliviously identified. We proposed that the gut microbiota directly participated in AFB1-induced liver pyroptosis and inflammation. These results provide new insights into the mechanisms of AFB1 hepatotoxicity and pave a window for new targeted interventions to prevent or reduce AFB1 hepatotoxicity.

This study investigated the reproductive traits of the hermaphroditic four-finger threadfin, Eleutheronema tetradactylum, along the coasts of Thailand during January to December 2021. Fish samples were collected from Pattani Bay, Thailand to assess the sex ratio, gonadosomatic index (GSI), maturity stage and fecundity. Additional fish samples were also collected from other areas to evaluate the length and weight at first sex change (Ls50 and Ws50) and length at first maturity (Lm50). The overall sex ratio for male and female was 1:0.69 with male being predominant throughout the year. Threadfin fish spawn the whole year round with peaks during moderate rainy and heavy rainy seasons. Histological examination confirmed its protandrous hermaphrodite posing multiple spawning habits. The average fecundity was 1.85 × 105 ± 1.05 × 105 eggs and positively related with standard length, body weight, gonad weight, and egg diameter (p < 0.05). The Ls50 and Ws50 were 27.58 cm and 419.39 g, and 29.71 cm and 457.28 g, for fish from Pattani Bay and Samut Prakan province, respectively. The Lm50 of male from Pattani Bay and Samut Prakan province were 25.78 cm and 25.56 cm, respectively, which were larger than those from Satun and Nakhon Sri Thammarat provinces. The Lm50 of females from Pattani Bay was smaller than that from Samut Prakan province. This study provided fundamental information on the reproductive characteristics of E. tetradactylum, which can be implemented to support management of natural fish stock and aquaculture development.

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.

Danggui Buxue Tang (DBT) is a well-known Chinese herbal recipe often prescribed in clinical treatment for menopausal and cardiovascular symptoms. 5-Fluorouracil (5-FU) is a chemotherapy drug that treats several cancers; however, it causes severe adverse effects and multidrug resistance. Combining natural medications can reduce the side effects of 5-FU use. Hence, we aimed to determine the role of DBT in strengthening the anticancer capabilities of 5-FU in a cultured colorectal adenocarcinoma cell line (HT-29 cell) and xenograft nude mice. HT-29 cells cultured with DBT did not exhibit cytotoxicity. However, co-administration of DBT with 5-FU significantly increased apoptosis and the expression of apoptotic markers. The inhibition of proliferation induced by DBT and 5-FU was shown to be mediated by c-Jun N-terminal kinase signaling. In addition, the potentiation effect of 5-FU and DBT was demonstrated in reducing tumor size, expressions of Ki67 and CD34 in HT-29 xenograft mice. This finding suggests that DBT can work with 5-FU as a novel chemotherapeutic strategy for treating colon cancer.

This study assessed the feeding habits of four-finger threadfin fish, Eleutheronema tetradactylum, and its diet relationship with other fish species in the tropics. Fish samples were collected from four locations along the coastal regions of Thailand. A whole year field sampling event was conducted to investigate the diet relationship of threadfin fish with other ten co-existing fish species in Pattani Bay during January 2021 and January 2022. E. tetradactylum was an active and specific predator with significant diet shift during ontogeny. Specifically, the juvenile fish fed largely on zooplankton especially Acetes/shrimp postlarvae, and small sized-fish fed on penaeid shrimps, while medium and large-sized fish shifted their diets to a combination of penaeid shrimp, fish and squid. Size and sex of fish as well as site of collection significantly affected gut fullness index and average number of food type (p < 0.05). Transitional sex fish predated almost entirely on other fishes (87.2%), whereas male and female fish fed mainly on penaeid shrimp (66.5%) and other fish (51.3%), respectively. Fish size and mouth opening controlled the size of prey, with the larger fish with larger mouth-opening fed primarily on the larger size of prey. Moreover, E. tetradactylum shared its diets inclusively with Epinephelus coioides, Johnius belangerii, Scomberomorus commerson, Scomberoides lysan, Otolithes ruber and Lutjanus russelli. Penaeid shrimp and teleost fish were the main food types shared by these fishes. This study provided important information on the feeding habits of E. tetradactylum and its diet relationship with other co-existing fish species living in the same habitat of a tropical coastal region.

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 hip-pocampus. 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 neu-rotransmitters, 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.

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.

The root of Scutellaria baicalensis is being used as herbal medicine, while its stem and leaf (aerial part) are considered as waste. The extract of aerial part of S. baicalensis, named as SBA here, has been shown to replace antibiotics in farming of Siganus fuscescens (rabbit fish), as to fight against marine pathogenic bacteria. To support the usage of SBA as feeding for aquaculture, the gut microbiota, after intake of the herbal extract, was determined. Here, the extract of SBA was mixed into the feeding of S. fuscescens that was cultured with a mixture of pathogenic bacteria. After 2 days of feeding, the gut content of fish was collected for the extraction and sequenced of 16S rDNA. The results indicated that the intake of SBA extract showed strong anti-bacterial effect, which inhibited the growth of pathogenic bacteria, i.e., Deltaproteobacteria and Fusobacteria. In contrast to antibiotic (enrofloxacin), the growth of probiotics, e.g., Erysipelotrichia, was promoted after intake of SBA. Our investigations showed the anti-bacterial effect of SBA extract in vivo, as well as its potential effect to promote the uptake of nutrients. The superiority of using this herbal extract in comparing to antibiotic was illustrated here, and which further suggested the possible development of recycling the waste product of S. baicalensis in fish aquaculture.

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 alpha 7 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 alpha 7 nAChR agonist. By contrast, the antagonist of alpha 7 nAChR was able to fully block the UV-induced phagocytosis, suggesting the role of alpha 7 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 alpha 7 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 alpha 7 nAChR antagonist. The result suggests that the cholinergic system, especially alpha 7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.