Picroside II

Picroside II (Pic II) has been used to treat many skeletal diseases. Postmenopausal osteoporosis (PMOP) is a serious skeletal disease that significantly threatens the health of postmenopausal women. We aimed to explore the roles and mechanisms of Pic II in PMOP. PMOP models were established by performing bilateral ovariectomy in rats and stimulating osteoblasts with H₂O₂. In vivo, micro-CT imaging, HE and MASSON staining were performed, and E₂, Ca/Cre, ALP, BGP, SOD, MDA, Fe²⁺ and ROS levels were determined. In vitro, cell viability, apoptosis, mineralization, GSH and Fe²⁺ levels were measured. Both animal and cell experiments detected the expressions of YY1, TGFβ1, SLC7A11, GPX4, RunX2 and BMP2 proteins. Moreover, PMOP cells were treated with N-Acetyl-L-cysteine (a ferroptosis inhibitor) to further explore the mechanisms of Pic II on PMOP. Pic II attenuated bone loss, improved femur pathological injury and increased collagen volume fraction for PMOP rats. Furthermore, after Pic II treatment, PMOP rats exhibited decreased Ca/Cre, ALP, MDA, Fe²⁺ and ROS levels, but increased E₂, BGP and SOD levels. In vitro, Pic II intervention elevated cell viability, GSH level and mineralization, suppressed apoptosis, and reduced ROS and Fe²⁺ levels. Moreover, both animal and cell experiments observed that Pic II upregulated YY1, GPX4, SLC7A11, Runx2 and BMP2 expressions, but downregulated TGFβ1 expression. Importantly, Pic II exhibited similar effects to N-Acetyl-L-cysteine in PMOP cells. Pic II may regulate YY1/TGFβ1 axis by inhibiting osteoblast ferroptosis to alleviate PMOP, suggesting that Pic II may be a novel agent for PMOP treatment.

Fever is characterized by an upregulation of the thermoregulatory set‐point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)‐induced fever model in Wistar rats.

Active phytoconstituents of Fevogrit were identified and quantified using ultra‐high‐performance liquid chromatography (UHPLC) platform. For the in‐vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6‐h time point, levels of TNF‐α, IL‐1β and IL‐6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post‐LPS administration.

UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti‐inflammatory properties. Fevogrit treatment efficiently reduces the LPS‐induced rise in the rectal temperature of animals. The levels and gene expression of TNF‐α, IL‐1β and IL‐6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment.

The findings of the study demonstrated that Fevogrit can suppress LPS‐induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection‐induced increase in body temperatures.