f immunomodulation activities, which was through regulation of inflammatory mediators via MAPK and PI3K/Akt signaling pathways.
The abnormal proliferation and differentiation of cardiac fibroblasts (CFs) are universally regarded as the key process for the progressive development of cardiac fibrosis following various cardiovascular diseases. Huoxin Pill (Concentrated pill, HXP) is a Chinese herbal formula for treating coronary heart disease. However, the cellular and molecular mechanisms of HXP in the treatment of myocardial fibrosis are still unclear.
To investigate the effects of HXP on CFs transdifferentiation and collagen synthesis under isoproterenol (ISO) conditions, as well as the potential mechanism of action.
In vivo, we established a rat model of cardiac fibrosis induced by ISO, and administered with low or high dose of HXP (10mg/kg/day or 30mg/kg/day). The level of α-SMA was detected by immunohistochemistry examination, and combined with RNA-sequencing analysis to determine the protective effect of HXP on myocardial fibrosis rats. In vitro, by culturing primary rat CFs, we examined the effects of HXP on the proliferatimay be a new therapeutic tool for cardiac fibrosis.
HXP suppresses ISO-induced CFs transdifferentiation and collagen synthesis, and it may exert these effects in part by inhibiting the activation of the TGF-β/Smads pathway. This may be a new therapeutic tool for cardiac fibrosis.
The population has traditionally used the Mangifera indica plant leaves to treat diseases such as Diabetes Mellitus and alleviate signs and symptoms such as inflammation, diarrhea, and dysentery. In a previous study, we demonstrated that the flavonoids present in the aqueous extract from M. indica leaves (EAMI) exhibited a potent hypoglycemic effect in diabetic rats, promoting the widespread use of the plant by the population and highlighting the importance of investigating its oral toxicity.
The present study aimed to assess the toxic potential of EAMI in rats submitted to experimental models of acute and subacute (short-term) oral toxicity.
For the acute toxicity test, female Wistar rats received a single oral dose of 2000mg/kg body weight of EAMI and were observed for 14 days. In the short-term toxicity test, male and female Wistar rats received repeated oral EAMI doses of 125, 250, 500 or 1000mg/kg body weight and observed for 28 days.
The phytochemical analysis of EAMI demonstrated that the extract has high levels of flavonoids. No animals died in the acute toxicity test, and no clinical changes were observed that show signs of toxicity in the animals. There was no significant change in the weight of the organs of the animals submitted to tests with the EAMI, suggesting that LD
is greater than 2000mg/kg. In the conditions and doses tested in the short-term toxicity experiments, the treatment did not produce significant changes in the physiological, biochemical, hematological, and histopathological parameters in the animals evaluated.
Our study demonstrated that high doses of EAMI administered acutely, as well as all doses evaluated in the short-term oral toxicity model, should be considered safe during traditional therapeutic use.
Our study demonstrated that high doses of EAMI administered acutely, as well as all doses evaluated in the short-term oral toxicity model, should be considered safe during traditional therapeutic use.
Terminalia chebula (TC), a well-known Indian Ayurvedic medicine introduced into China in the Sui and Tang Dynasties, has been recorded and used medicinally as Fructus Chebulae, together with its variety tomentella (TCT) in the Chinese Pharmacopoeia. They have been also used commonly for the treatment of diabetes mellitus by Tibetan medicine.
To investigate the main bioactive and therapeutic principles in the fruits of TCT, based on the extensive evaluation of their anti-inflammatory and hypoglycemic activities.
The TCT fresh fruits were analyzed by HPLC and separated further by column chromatography and preparative HPLC. The isolated compounds were identified by extensive spectroscopic analyses, including 1D/2D NMR, MS, UV, IR and ECD. https://www.selleckchem.com/products/lyn-1604.html Anti-inflammatory activity was evaluated by inhibition of NO production in RAW264.7cells. The specific iNOS (PDB ID 3E7G) structure was prepared by Discovery Studio 4.0, and the molecular docking simulation was performed on GOLD (version 5.2.2). Hypoglycemic activity was rolyzed tannins are the main active ingredients of TCT fruits, responsible for the traditional treatment of sore throat and cough. Moreover, hydrolyzed tannins and simple phenolic compounds with potential hypoglycemic activity are closely related to the ethno-pharmacological uses of TCT fruits on diabetes in Tibetan medicine.Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision ( less then 5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy.
f immunomodulation activities, which was through regulation of inflammatory mediators via MAPK and PI3K/Akt signaling pathways.
The abnormal proliferation and differentiation of cardiac fibroblasts (CFs) are universally regarded as the key process for the progressive development of cardiac fibrosis following various cardiovascular diseases. Huoxin Pill (Concentrated pill, HXP) is a Chinese herbal formula for treating coronary heart disease. However, the cellular and molecular mechanisms of HXP in the treatment of myocardial fibrosis are still unclear.
To investigate the effects of HXP on CFs transdifferentiation and collagen synthesis under isoproterenol (ISO) conditions, as well as the potential mechanism of action.
In vivo, we established a rat model of cardiac fibrosis induced by ISO, and administered with low or high dose of HXP (10mg/kg/day or 30mg/kg/day). The level of α-SMA was detected by immunohistochemistry examination, and combined with RNA-sequencing analysis to determine the protective effect of HXP on myocardial fibrosis rats. In vitro, by culturing primary rat CFs, we examined the effects of HXP on the proliferatimay be a new therapeutic tool for cardiac fibrosis.
HXP suppresses ISO-induced CFs transdifferentiation and collagen synthesis, and it may exert these effects in part by inhibiting the activation of the TGF-β/Smads pathway. This may be a new therapeutic tool for cardiac fibrosis.
The population has traditionally used the Mangifera indica plant leaves to treat diseases such as Diabetes Mellitus and alleviate signs and symptoms such as inflammation, diarrhea, and dysentery. In a previous study, we demonstrated that the flavonoids present in the aqueous extract from M. indica leaves (EAMI) exhibited a potent hypoglycemic effect in diabetic rats, promoting the widespread use of the plant by the population and highlighting the importance of investigating its oral toxicity.
The present study aimed to assess the toxic potential of EAMI in rats submitted to experimental models of acute and subacute (short-term) oral toxicity.
For the acute toxicity test, female Wistar rats received a single oral dose of 2000mg/kg body weight of EAMI and were observed for 14 days. In the short-term toxicity test, male and female Wistar rats received repeated oral EAMI doses of 125, 250, 500 or 1000mg/kg body weight and observed for 28 days.
The phytochemical analysis of EAMI demonstrated that the extract has high levels of flavonoids. No animals died in the acute toxicity test, and no clinical changes were observed that show signs of toxicity in the animals. There was no significant change in the weight of the organs of the animals submitted to tests with the EAMI, suggesting that LD
is greater than 2000mg/kg. In the conditions and doses tested in the short-term toxicity experiments, the treatment did not produce significant changes in the physiological, biochemical, hematological, and histopathological parameters in the animals evaluated.
Our study demonstrated that high doses of EAMI administered acutely, as well as all doses evaluated in the short-term oral toxicity model, should be considered safe during traditional therapeutic use.
Our study demonstrated that high doses of EAMI administered acutely, as well as all doses evaluated in the short-term oral toxicity model, should be considered safe during traditional therapeutic use.
Terminalia chebula (TC), a well-known Indian Ayurvedic medicine introduced into China in the Sui and Tang Dynasties, has been recorded and used medicinally as Fructus Chebulae, together with its variety tomentella (TCT) in the Chinese Pharmacopoeia. They have been also used commonly for the treatment of diabetes mellitus by Tibetan medicine.
To investigate the main bioactive and therapeutic principles in the fruits of TCT, based on the extensive evaluation of their anti-inflammatory and hypoglycemic activities.
The TCT fresh fruits were analyzed by HPLC and separated further by column chromatography and preparative HPLC. The isolated compounds were identified by extensive spectroscopic analyses, including 1D/2D NMR, MS, UV, IR and ECD. https://www.selleckchem.com/products/lyn-1604.html Anti-inflammatory activity was evaluated by inhibition of NO production in RAW264.7cells. The specific iNOS (PDB ID 3E7G) structure was prepared by Discovery Studio 4.0, and the molecular docking simulation was performed on GOLD (version 5.2.2). Hypoglycemic activity was rolyzed tannins are the main active ingredients of TCT fruits, responsible for the traditional treatment of sore throat and cough. Moreover, hydrolyzed tannins and simple phenolic compounds with potential hypoglycemic activity are closely related to the ethno-pharmacological uses of TCT fruits on diabetes in Tibetan medicine.Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision ( less then 5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy.
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