Ni-Catalyzed Reductive Dibenzylation of Trifluoromethylalkenes for CF3-Containing All-Carbon Quaternary Center Construction.

A Ni-catalyzed reductive dicarbofunctionalization of α-CF3 styrenes with benzyl bromides has been accomplished. This transformation obviates the commonly facile ß-F elimination effectively and enables the creation of CF3-substituted all-carbon quaternary centers of pharmaceutical interests. Preliminary mechanistic studies suggest a pathway consisting of benzyl radical addition and subsequent nickel-mediated benzylation of the resulting α-CF3-embedded tertiary C radical.

Brain targeted borneol-baicalin liposome improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury via inhibiting HIF-1α/VEGF/eNOS/NO signal pathway.

Baicalin (BA) is widely used in the treatment of cerebral ischemia-reperfusion injury (CIRI). The key to treating encephalopathy is to increase the amounts of drugs entering the brain. Borneol-baicalin liposome (BO-BA-LP) was prepared in previous research based on the characteristics of borneol (BO) in promoting drug brain entry. In this study, the effect of BO-BA-LP on improving blood-brain barrier (BBB) integrity was researched. Results showed BO-BA-LP may increase ability of BA to penetrate the cell membrane in vitro. Pharmacokinetic results showed the BO-BA-LP could increase concentrations of BA in plasma and brain tissues of normal and CIRI mice. Pharmacological results revealed BO-BA-LP could improve the neurological function, brain edema, and histopathology of CIRI mice. Besides, BO-BA-LP could protect BBB by regulating hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. The research showed that BO in BO-BA-LP could increase the absorption of BA by increasing BBB permeability, leading to a better therapeutic effect of BO-BA-LP on CIRI mice.

Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy.

In recent years, there have been many exciting developments in the biomedical applications of the macrophage membrane bionic drug delivery system (MM-Bio-DDS). Macrophages, as an important immune cell, are involved in initiating and regulating the specific immune response of the body. Therefore, the inflammatory process related to macrophages is an important goal in the diagnosis and treatment of many diseases. In this review, we first summarise the different methods of preparation, characterisation, release profiles and natural advantages of using macrophages as a drug delivery system (DDS). Second, we introduce the processes of various chronic inflammatory diseases and the role of macrophages in them, specifically clarifying how the MM-Bio-DDS provides a wide and effective treatment for the targeted inflammatory site. Finally, based on the existing research, we propose the application prospect and existing challenges of the MM-Bio-DDS, especially the problems in clinical transformation, to provide new ideas for the development and utilisation of the MM-Bio-DDS in targeted drug delivery for inflammation and the treatment of diseases.

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders.

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer's disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

Medicine-food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis. Therefore, this review summarizes the pharmacological effects of AS for the treatment of AD and AD-complications for the first time. AS contains many effective components, such as ligustilide, z-ligustilide, n-butylidenephthalide, α-pinene, p-cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B12, folic acid, arginine, and oleic acid, which can improve the symptoms of AD. Besides, this review focuses on the safety and toxicity evaluation of AS, which provides a basis for its application. This review will provide further support for the research on AD and the application of medicine-food herb AS in a healthy lifestyle in the future.

Natural essential oils efficacious in internal organs fibrosis treatment: Mechanisms of action and application perspectives.

Internal organs fibrosis (IOF) is the leading cause of morbidity and mortality in most chronic inflammatory diseases, which is responsible for 45% of deaths due to disease. However, there is a paucity of drugs used to treat IOF, making it urgent to find medicine with good efficacy, low toxic side effects and good prognosis. Essential oils (EOs) extracted from natural herbs with a wide range of pharmacological components, multiple therapeutic targets, low toxicity, and broad sources have unique advantages and great potential in the treatment of IOF. In this review, we summarized EOs and their monomeric components with anti-IOF, and found that they work mainly through inhibiting TGF-ß-related signaling pathways, modulating inflammatory cytokines, suppressing NF-κB, and anti-oxidative stress. The prognostic improvement of natural EOs on IOF was further discussed, as well as the quality and safety issues in the current development of natural EOs. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in anti-IOF.

Natural essential oils: A promising strategy for treating cardio-cerebrovascular diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EO) are volatile compounds obtained from different parts of natural plants, and have been used in national, traditional and folk medicine to treat various health problems all over the world. Records indicate that in history, herbal medicines rich in EO have been widely used for the treatment of CVDs in many countries, such as China. AIM OF THE STUDY: This review focused on the traditional application and modern pharmacological mechanisms of herbal medicine EO against CVDs in preclinical and clinical trials through multi-targets synergy. Besides, the EO and anti-CVDs drugs were compared, and the broad application of EO was explained from the properties of drugs and aromatic administration routes. MATERIALS AND METHODS: Information about EO and CVDs was collected from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The obtained data sets were sequentially arranged for better understanding of EO' potential. RESULTS: The study showed that EO had significant application in CVDs at different countries or regions since ancient times. Aiming at the complex pathological mechanisms of CVDs, including intracellular calcium overload, oxidative stress, inflammation, vascular endothelial cell injury and dysfunction and dyslipidemia, we summarized the roles of EO on CVDs in preclinical and clinical through multi-targets intervention. Besides, EO had the dual properties of drug and excipients. And aromatherapy was one of the complementary therapies to improve CVDs. CONCLUSIONS: This paper reviewed the EO on traditional treatment, preclinical mechanism and clinical application of CVDs. As important sources of traditional medicines, EO' remarkable efficacy had been confirmed in comprehensive literature reports, which showed that EO had great medicinal potential.

Macrophage membrane modified baicalin liposomes improve brain targeting for alleviating cerebral ischemia reperfusion injury.

Baicalin (BA) has a good intervention effect on encephalopathy. In this study, macrophage membrane was modified on the surface of baicalin liposomes (BA-LP) by extrusion method. Macrophage membrane modified BA-LP (MM-BA-LP) was characterized by various analytical techniques, and evaluated for brain targeting. The results presented MM-BA-LP had better brain targeting compared with BA-LP. Pharmacokinetic experiments showed that MM-BA-LP improved pharmacokinetic parameters and increased the residence time of BA. Pharmacodynamic of middle cerebral artery occlusion (MCAO) rat model was studied to verify the therapeutic effect of MM-BA-LP on cerebral ischemia reperfusion injury (CIRI). The results showed that MM-BA-LP could significantly improve the neurological deficit, cerebral infarction volume and brain pathological state of MCAO rats compared with BA-LP. These results suggested that MM-BA-LP could significantly enhance the brain targeting and improve the circulation of BA in blood, and had a significantly better neuroprotective effect on MCAO rats than BA-LP.

Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies.

Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration.

Borneol in cardio-cerebrovascular diseases: Pharmacological actions, mechanisms, and therapeutics.

With the coming acceleration of global population aging, the incidence rate of cardio-cerebrovascular diseases (CVDs) is increasing. It has become the leading cause of human mortality. As a natural drug, borneol (BO) not only has anti-inflammatory, anti-oxidant, anti-apoptotic, anti-coagulant activities and improves energy metabolism but can also promote drugs to enter the target organs or tissues through various physiological barriers, such as the blood-brain barrier (BBB), mucous membrane, skin. Thus, it has a significant therapeutic effect on various CVDs, which has been confirmed in a large number of studies. However, the pharmacological actions and mechanisms of BO on CVDs have not been fully investigated. Hence, this review summarizes the pharmacological actions and possible mechanisms of BO, which provides novel ideas for the treatment of CVDs.

A novel technology to reduce astringency of tea polyphenols extract and its mechanism.

Objective: Tea polyphenols are natural extracts used widely throughout the world. However, the severe astringency of tea polyphenols has reduced patient compliance. Based on the analysis of the formation mechanism of astringency, this paper hopes to propose a new method to control the astringency of tea polyphenols and improve patient compliance without changing its effect. Methods: Artificial saliva was used to prepare the tea polyphenols solution with different pH, using ß-casein to imitate salivary protein, and preparing 1.2 mg/mL ß-casein solution. A fluorescence quenching test was used to study the interaction between tea polyphenols and ß-casein, combined with the stability test results of the compound, we can choose the pH with weak binding but good stability as the best pH for masking astringency. The taste-masking tablets were prepared under the best pH conditions, and the Xinnaojian Original Tablets were prepared according to the conventional preparation method. The disintegration time limit and solubility were tested respectively. The astringency of Xinnaojian original tablets and taste-masking tablets was evaluated by visual analogue scale (VAS). Results: The result of the fluorescence quenching test prompted that the combination force was the weakest when the pH was 4.9. Further synchronous fluorescence analysis showed that an increase in pH resulted in a decrease of the binding sites between tea polyphenols and ß-casein, and this decrease was closely related to changes in tryptophan residues in ß-casein. Both original and taste-masking Xinnaojian Tablets were prepared. Volunteers' VAS scores illustrated that the astringency improved significantly with the masking tablets (P < 0.05). Conclusion: This pH-adjusting masking treatment had little effect on the recovery of polyphenols from the tablets or the dissolution of the tablets. This study provides a novel and feasible astringency masking technology for tea polyphenols and its preparation.

Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder.

Depression is a common global mental disorder that seriously harms human physical and mental health. With the development of society, the increase of pressure and the role of various other factors make the incidence of depression increase year by year. However, there is a lack of drugs that have a fast onset, significant effects, and few side effects. Some volatile oils from traditional natural herbal medicines are usually used to relieve depression and calm emotions, such as Lavender essential oil and Acorus tatarinowii essential oil. It was reported that these volatile oils, are easy to enter the brain through the blood-brain barrier and have good antidepressant effects with little toxicity and side effects. In this review, we summarized the classification of depression, and listed the history of using volatile oils to fight depression in some countries. Importantly, we summarized the anti-depressant natural volatile oils and their monomers from herbal medicine, discussed the anti-depressive mechanisms of the volatile oils from natural medicine. The volatile oils of natural medicine and antidepressant drugs were compared and analyzed, and the application of volatile oils was explained from the clinical use and administration routes. This review would be helpful for the development of potential anti-depressant medicine and provide new alternative treatments for depressive disorders.

Research Advances in Cardio-Cerebrovascular Diseases of Ligusticum chuanxiong Hort.

Cardio-cerebrovascular diseases (CVDs) are a serious threat to human health and account for 31% of global mortality. Ligusticum chuanxiong Hort. (CX) is derived from umbellifer plants. Its rhizome, leaves, and fibrous roots are similar in composition but have different contents. It has been used in Japanese, Korean, and other traditional medicine for over 2000 years. Currently, it is mostly cultivated and has high safety and low side effects. Due to the lack of a systematic summary of the efficacy of CX in the treatment of CVDs, this article describes the material basis, molecular mechanism, and clinical efficacy of CX, as well as its combined application in the treatment of CVDs, and has been summarized from the perspective of safety. In particular, the pharmacological effect of CX in the treatment of CVDs is highlighted from the point of view of its mechanism, and the complex mechanism network has been determined to improve the understanding of CX's multi-link and multi-target therapeutic effects, including anti-inflammatory, antioxidant, and endothelial cells. This article offers a new and modern perspective on the impact of CX on CVDs.

Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-κB Pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are challenging diseases with the high mortality in a clinical setting. Baicalin (BA) is the main effective constituent isolated from the Chinese medical herb Scutellaria baicalensis Georgi, and studies have proved that it has a protective effect on ALI induced by lipopolysaccharide (LPS) due to the anti-inflammatory efficacy. However, BA has low solubility which may limit its clinical application. Hence, we prepared a novel drug delivery system-Baicalin liposome (BA-LP) in previous research-which can improve some physical properties of BA. Therefore, we aimed to explore the effect of BA-LP on ALI mice induced by LPS. In pharmacokinetics study, the values of t 1/2 and AUC0- t in the BA-LP group were significantly higher than that of the BA group in normal mice, indicating that BA-LP could prolong the duration time in vivo of BA. The BA-LP group also showed a higher concentration in lung tissues than the BA group. Pharmacodynamics studies showed that BA-LP had a better effect than the BA group at the same dosage on reducing the W/D ratio, alleviating the lung injury score, and decreasing the proinflammatory factors (TNF-α, IL-1ß) and total proteins in bronchoalveolar lavage fluids (BALF). In addition, the therapeutic effects of BA-LP showed a dose-dependent manner. Western blot analysis indicated that the anti-inflammatory action of BA could be attributed to the inhibition of the TLR4-NFκBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.

Preparation, Characterization and in vivo Study of Borneol-Baicalin-Liposomes for Treatment of Cerebral Ischemia-Reperfusion Injury.

PURPOSE: Baicalin (BA) has a good neuroprotective effect, but it is eliminated quickly in the body and does not easily reach the brain. In this experiment, borneol (BO) was used as an auxiliary drug to prepare borneol-baicalin-liposomes (BO-BA-LP) to prolong the efficacy time of BA, synergistically synergize, introduce drugs into the brain, and better exert the therapeutic effect on cerebral ischemia-reperfusion (I/R) injury. METHODS: Through single-factor inspection and response surface optimization analysis, obtained the best preparation process of BO-BA-LP and characterized by various analytical techniques. Validated the long-term effectiveness of BA-BO-LP through pharmacokinetic studies and conducted pharmacodynamic studies on the middle cerebral artery occlusion (MCAO) rat model to verify the therapeutic effect of BO-BA-LP on cerebral I/R injury. RESULTS: The optimum preparation conditions of BO-BA-LP were as follows: the dosage of BO was 9.55 mg, the ratio of phospholipid to drug was 4.02:1, the ratio of phospholipid to cholesterol was 7.25:1, the entrapment efficiency (EE) was 41.49%, and the drug loading (DL) was 4.29%. The particle size range of the liposomes was 167.1 nm, and the polydispersity index (PDI) range was 0.113. The results of pharmacokinetic experiments showed that the combination of BA and BO liposomes effectively improved the pharmacokinetic parameters of BA and prolonged the half-life of BA. Pharmacodynamic studies have found that, compared with BA-LP, BO-BA-LP can significantly improve neurological deficits, cerebral infarction volume, and brain pathological states on MCAO rats. CONCLUSION: These results demonstrated that BO-BA-LP can improve the circulation of drugs in the blood, and the addition of BO can enhance the therapeutic effect of BA and effectively improve cerebral I/R.

Nose to brain drug delivery - A promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion.

Cerebral ischemia reperfusion injury (CIRI), one of the major causes of death from stroke in the world, not only causes tremendous damage to human health, but also brings heavy economic burden to society. Current available treatments for CIRI, including mechanical therapies and drug therapies, are often accompanied by significant side-effects. Therefore, it is necessary to discovery new strategies for treating CIRI. Many studies have confirmed that the herbal medicine has the advantages of abundant resources, good curative effect and little side effects, which can be used as potential drug for treatment of CIRI through multiple targets. It's known that oral administration commonly has low bioavailability, and injection administration is inconvenient and unsafe. Many drugs can't delivery to brain through routine pathways due to the blood-brain-barrier (BBB). Interestingly, increasing evidences have suggested the nasal administration is a potential direct route to transport drug into brain avoiding the BBB and has the characteristics of high bioavailability for treating brain diseases. Therefore, intranasal administration can be treated as an alternative way to treat brain diseases. In the present review, effective methods to treat CIRI by using active ingredients derived from herbal medicine through nose to brain drug delivery (NBDD) are updated and discussed, and some related pharmacological mechanisms have also been emphasized. Our present study would be beneficial for the further drug development of natural agents from herbal medicines via NBDD.