Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19.

Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.

Ginseng total saponins and Fuzi total alkaloids exert antidepressant-like effects in ovariectomized mice through BDNF-mTORC1, autophagy and peripheral metabolic pathways.

BACKGROUND: Shenfu decoction (SFD) is a classic Chinese medicine prescription that has a strong cardiotonic effect. The combination of ginseng (the dried root of Panax ginseng C. A. Meyer) and Fuzi (processed product of sub-root of Aconitum carmichaeli Debx), the main constituents of SFD, has been reported to improve the pharmacological effect of each other. Moreover, research has shown that the main active components of SFD, ginseng total saponins (GTS) and Fuzi total alkaloids (FTA), have antidepressant activity. However, the effects of these ingredients on depressive-like behavior induced by ovariectomy, a model of menopausal depression, have not been studied. PURPOSE: Our research aims to elucidate the antidepressant-like effects of GTS and FTA compatibility (GF) in ovariectomized mice and the potential mechanisms. METHODS: To elucidate the antidepressant-like effects of GF in mice in ovariectomy condition, behavioral tests were performed after 7 days of intragastric administration of different doses of GF. Underlying molecular mechanisms of CREB-BDNF, BDNF-mTORC1 and autophagy signaling were detected by western blotting, serum metabolites were examined by UPLC-QE plus-MS and dendritic spine density was determined by Golgi-Cox staining. RESULTS: GF remarkably decreased the immobility time in the forced swim test. GF also increased levels of pCREB/CREB, BDNF, Akt, mTORC1 and p62 in the prefrontal cortex and hippocampus, as well as decreased LC3-II/LC3-I in the prefrontal cortex and hippocampus of ovariectomized mice. Furthermore, 15 serum differential metabolites (9 of which are lipids and lipid molecules) were identified by metabonomics. Next, the antidepressant-like effects of GF was blocked by rapamycin, an inhibitor of mTORC1. The antidepressant actions of GF on levels of pCREB, mTORC1, LC3-Ⅱ/LC3-Ⅰ and p62 in the prefrontal cortex and the levels of BDNF, Akt, mTORC1 and p62 in the hippocampus were inhibited by rapamycin, and the dendritic spines density was also regulated. CONCLUSION: GF has antidepressant effects in ovariectomized mice, and like other antidepressants, these effects involve activation of BDNF-mTORC1, autophagy regulation and consequent effects on hippocampal synaptic plasticity. Moreover, metabolomic results suggest that GF also has effects on peripheral lipid profiles that may provide potential biomarkers for these antidepressant-like effects. These results indicate that GF is worthy of further exploration as a promising pharmaceutical treatment for depression. This study provides a new direction for the development of new indications for traditional Chinese medicine compounds.

Berberine: A Promising Treatment for Neurodegenerative Diseases.

Berberine, as a natural alkaloid compound, is characterized by a diversity of pharmacological effects. In recent years, many researches focused on the role of berberine in central nervous system diseases. Among them, the effect of berberine on neurodegenerative diseases has received widespread attention, for example Alzheimer's disease, Parkinson's disease, Huntington's disease, and so on. Recent evidence suggests that berberine inhibits the production of neuroinflammation, oxidative, and endoplasmic reticulum stress. These effects can further reduce neuron damage and apoptosis. Although the current research has made some progress, its specific mechanism still needs to be further explored. This review provides an overview of berberine in neurodegenerative diseases and its related mechanisms, and also provides new ideas for future research on berberine.

Mechanisms of paeoniaceae action as an antidepressant.

Paeoniflorin (PF) has been widely used for the treatment of depression in mice models, some Chinese herbal compound containing PF on treating depression, such as Xiaoyao San, Chaihu-Shugan-San, Danggui Shaoyao San etc. Many experiments are also verifying whether PF in these powders can be used as an effective component in the treatment of depression. Therefore, in this review the antidepressant effect of PF and its mechanism of action are outlined with particular focus on the following aspects: increasing the levels of monoamine neurotransmitters, inhibiting the HPA axis, promoting neuroprotection, enhancing neurogenesis in the hippocampus, and elevating levels of brain-derived neurotrophic factor (BDNF). This review may be helpful for the application of PF in the treatment of depression.

KLF4 Exerts Sedative Effects in Pentobarbital-Treated Mice.

KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell proliferation, and apoptosis. Through effects on these processes, KLF4 has likely roles in Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, little is known about the role of KLF4 in more immediate behavioral processes that similarly depend upon broad changes in brain excitability, such as the sleep process. Here, behavioral approaches, western blot, and immunohistochemical experiments were used to explore the role of KLF4 on sedation and the potential mechanisms of those effects. The results showed that overexpression of KLF4 prolonged loss of righting reflex (LORR) duration in pentobarbital-treated mice and increased c-Fos expression in the lateral hypothalamus (LH) and the ventrolateral preoptic nucleus (VLPO), while it decreased c-Fos expression in the tuberomammillary nucleus (TMN). Moreover, overexpression of KLF4 reduced the expression of p53 in the hypothalamus and increased the expression of STAT3 in the hypothalamus. Therefore, these results suggest that KLF4 exerts sedative effects through the regulation of p53 and STAT3 expression, and it indicates a role of KLF4 ligands in the treatment of sleep disorders.

Effects of Ginseng on Neurological Disorders.

Ginseng (Panax ginseng Meyer), a famous traditional medicinal herb, has been widely used for many centuries. Numerous studies have shown that ginseng has a positive effect on the prevention and treatment of neurological disorders. In this review, we summarized the effects of ginseng in treating neurological diseases, particularly the anti-depressant effects of ginseng. Furthermore, its potential mechanism was also outlined. Therefore, this review may provide new insight into the treatment of ginseng on neurological diseases.

Anti-ageing effects of red ginseng on female Drosophila melanogaster.

Red ginseng (RG) was recently reported to extend the lifespan of Drosophila melanogaster. However, the mechanism underlying this effect has not yet been elucidated. The present study aimed to elucidate the molecular mechanisms of the RG-mediated prolongation of the lifespan of female D melanogaster. In this study, protein changes in 36-day-old female D melanogaster were identified using isobaric tag for relative and absolute quantitation (iTRAQ), and levels of differentially expressed proteins were verified by quantitative real-time PCR and Western blotting. Our studies have shown that RG concentrations of 12.5, 15 and 17.5 mg/mL significantly prolonged the lifespan. Eleven proteins were up-regulated and 46 were down-regulated between the RG and control groups; and Pebp1 expression was significantly down-regulated. In addition, AKT and p-AKT were down-regulated, and ERK, p-ERK and Raf1 were up-regulated by RG. Therefore, RG significantly prolonged the lifespan of female D melanogaster by reducing the expression of Pebp1, up-regulating ERK and inhibiting the AKT pathway. RG may be a potential drug for anti-ageing treatment.

Neuropharmacological effects of Aconiti Lateralis Radix Praeparata.

Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), which are the lateral roots of Aconitum Carmichaelii Debx, is widely used in China to treat many neurological diseases. Fuzi, in its various forms, has many neuropharmacological effects. It can act as an analgesic and help with depression, epilepsy, and dementia. However, the neuropharmacological effects of Aconiti Lateralis Radix Praeparata are seldom comprehensively reviewed. In this review, the neuropharmacological activities of some components contained in Aconiti Lateralis Radix Praeparata are considered. These include aconitine, mesaconitine, hypaconitine, total alkaloid, polysaccharide-1, benzoylmesaconine, fuziline, songorine, and napelline. We also specifically discuss the antidepressant effects of total alkaloids and polysaccharide-1. This review may provide a theoretical basis for further utilization of Aconiti Lateralis Radix Praeparata for diseases that affect the central nervous system.

Mechanisms of Panax ginseng action as an antidepressant.

OBJECTIVES: Panax ginseng, a well-known traditional Chinese medicine with multiple pharmacological activities, plays a crucial role in modulating mood disorders. Several recent studies have identified an underlying role of Panax ginseng in the prevention and treatment of depression. However, the cellular and molecular mechanisms remain unclear. MATERIALS AND METHODS: In this review, we summarized the recent progress of antidepressant effects and underlying mechanisms of Panax ginseng and its representative herbal formulae. RESULTS: The molecular and cellular mechanisms of Panax ginseng and its herbal formulae include modulating monoamine neurotransmitter system, upregulating the expression of neurotrophic factors, regulating the function of HPA axis, and anti-inflammatory action. CONCLUSIONS: Therefore, this review may provide theoretical bases and clinical applications for the treatment of depression by Panax ginseng and its representative herbal formulae.

Pharmacological effects of berberine on mood disorders.

Berberine, a natural isoquinoline alkaloid, is used in herbal medicine and has recently been shown to have efficacy in the treatment of mood disorders. Furthermore, berberine modulates neurotransmitters and their receptor systems within the central nervous system. However, the detailed mechanisms of its action remain unclear. This review summarizes the pharmacological effects of berberine on mood disorders. Therefore, it may be helpful for potential application in the treatment of mood disorders.

Recent Advances in Herbal Medicines for Digestive System Malignancies.

Herbal medicines, as an important part of traditional Chinese medicine (TCM), have been used to treat digestive system malignancies (DSM) for many years, and have gradually gained recognition worldwide. The role of herbal medicines in the comprehensive treatment of DSM is being improved from adjuvant treatment of the autologous immune function in cancer patients, to the treatment of both the symptoms and disease, direct inhibition of tumor cell growth and proliferation, and induction of tumor cell autophagy and apoptosis. Their specific mechanisms in these treatments are also being explored. The paper reviews the current anti-tumor mechanisms of TCM, including single herbal medicines, Chinese herbal formulations, Chinese medicine preparations and TCM extract, and their application in the comprehensive treatment of digestive system tumors, providing a reference for clinical application of TCM.

Leptin in depression: a potential therapeutic target.

Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies have identified an underlying role for leptin in regulation of mood and cognition via regulation of synaptic changes in the brain that have been associated with antidepressant-like actions. Brain neural plasticity occurs in response to a range of intrinsic and extrinsic stimuli, including those that may mediate the effects of antidepressants. Neural plasticity theories of depression are thought to explain multiple aspects of depression and the effects of antidepressants. It is also well documented that leptin has effects on neural plasticity. This review summarizes the recent literature on the role of leptin in neural plasticity in order to elaborate the possible mechanism of leptin's antidepressant-like effects. Recent findings provide new insights into the underlying mechanisms of neural plasticity in depression. Leptin may influence these mechanisms and consequently constitute a possible target for novel therapeutic approaches to the treatment of depression.

Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity.

Preclinical and clinical studies have demonstrated that zinc possesses antidepressant properties and that it may augment the therapy with conventional, that is, monoamine-based, antidepressants. In this review we aim to discuss the role of zinc in the pathophysiology and treatment of depression with regard to the monoamine hypothesis of the disease. Particular attention will be paid to the recently described zinc-sensing GPR39 receptor as well as aspects of zinc deficiency. Furthermore, an attempt will be made to give a possible explanation of the mechanisms by which zinc interacts with the monoamine system in the context of depression and neural plasticity.

The role of 5-HT2c receptor on corticosterone-mediated food intake.

Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice. Both corticosterone and mCPP increased c-Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c-Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5-HT2c receptors and leptin may be involved in the effects of corticosterone-induced hyperphagia.

Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells.

Cepharanthine is a medicinal plant-derived natural compound which possesses potent anti-cancer properties. However, there is little report about its effects on lung cancer cells. In this study, we investigated the effects of cepharanthine on the cell viability and apoptosis in human non-small-cell lung cancer H1299 and A549 cells. It was found that cepharanthine inhibited the growth of H1299 and A549 cells in a dose-dependent manner which was associated with the generation of reactive oxygen species(ROS) and the dissipation of mitochondrial membrane potential (Δψm). These effects were markedly abrogated when cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, indicating that the apoptosis-inducing effect of cepharanthine in lung cancer cells was mediated by ROS. In addition, cepharanthine triggered apoptosis in non-small lung cancer cells via the upregulation of Bax, downregulation of Bcl-2 and significant activation of caspase-3 and PARP. These results provide the rationale for further research and preclinical investigation of cepharanthine's anti-tumor effect against human non-small-cell lung cancer.

Role of 5-HT3 receptor on food intake in fed and fasted mice.

BACKGROUND: Many studies have shown that 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the regulation of feeding behavior. However, the relative contribution of 5-HT3 receptor remains unclear. The present study was aimed to investigate the role of 5-HT3 receptor in control of feeding behavior in fed and fasted mice. METHODOLOGY/PRINCIPAL FINDINGS: Food intake and expression of c-Fos, tyrosine hydroxylase (TH), proopiomelanocortin (POMC) and 5-HT in the brain were examined after acute treatment with 5-HT3 receptor agonist SR-57227 alone or in combination with 5-HT3 receptor antagonist ondansetron. Food intake was significantly inhibited within 3 h after acute treatment with SR 57227 in fasted mice but not fed mice, and this inhibition was blocked by ondansetron. Immunohistochemical study revealed that fasting-induced c-Fos expression was further enhanced by SR 57227 in the brainstem and the hypothalamus, and this enhancement was also blocked by ondansetron. Furthermore, the fasting-induced downregulation of POMC expression in the hypothalamus and the TH expression in the brain stem was blocked by SR 57227 in the fasted mice, and this effect of SR 57227 was also antagonized by ondansetron. CONCLUSION/SIGNIFICANCE: Taken together, our findings suggest that the effect of SR 57227 on the control of feeding behavior in fasted mice may be, at least partially, related to the c-Fos expression in hypothalamus and brain stem, as well as POMC system in the hypothalamus and the TH system in the brain stem.

Anticonvulsant effects of Fuzi total alkaloid on pentylenetetrazole-induced seizure in mice.

We investigated the anticonvulsant effect of acute Fuzi total alkaloid (FTA) in seizure induced by the GABAA-receptor antagonist pentylenetetrazole (PTZ). FTA significantly increased the seizure latency and decreased the mortality in PTZ-treated mice. Administration of PTZ increased c-Fos expression in the hippocampus, medial prefrontal cortex, and piriform cortex; and this PTZ-induced effect was inhibited by FTA in a dose-dependent manner. Furthermore, the effects of FTA on PTZ-induced seizure and c-Fos expression were reversed by the GABAA/benzodiazepine receptor-selective antagonist flumazenil. These findings suggest that the anticonvulsant effects of FTA may be related to modulation of GABAA-benzodiazepine receptor complex.

Antidepressant-like effect of Fuzi total alkaloid on ovariectomized mice.

Recent studies in vivo and vitro have shown that Fuzi polysaccharide has an antidepressant-like effect. Polysaccharide and total alkaloid are the two most important components of Fuzi. However, little is known about the antidepressant-like effect of Fuzi total alkaloid. To investigate the antidepressant-like effect of Fuzi total alkaloid, behavioral studies were performed in the open field test and forced swimming test. Repeated intragastric administration of Fuzi total alkaloid for 7 days (10 mg/kg) to normal mice decreased immobility time compared to the vehicle group. Furthermore, repeated administration of Fuzi total alkaloid (10 or 30 mg/kg) to ovariectomized mice also decreased immobility time in a dose-dependent manner. However, these antidepressant-like behavioral effects were not simply due to locomotor hyperactivity. Further experiments showed that Fuzi total alkaloid enhanced the ratio of phospho-CREB/CREB (cAMP response element-binding) and BDNF (brain-derived neurotrophic factor) protein level in the frontal cortex and hippocampus in ovariectomized mice but not in normal mice. These results indicate that the CREB-BDNF pathway may be involved in the antidepressant-like effect of Fuzi total alkaloid in ovariectomized mice.

Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters.

Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced in hamsters through a combination treatment of 5-fluorouracil and mild abrasion of the cheek pouch. Each drug was administered topically to the oral mucosa of hamsters, and the process of healing of damaged oral mucositis was examined by measuring the size of the mucositis. Azulene ointment did not reduce the size of the mucositis compared with the vaseline-treated control group. Polaprezinc-sodium alginate suspension significantly improved the recovery from 5-fluorouracil-induced damage. In contrast, local treatment with dexamethasone exacerbated the mucositis markedly. These results suggested the healing effect of polaprezinc-sodium alginate suspension and the risk of steroids to severe oral mucositis induced by chemotherapy.