Rosmanol

Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway

Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor α (TNF-α). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg/kg/d each), the anti-RA effect and inhibitory activity on the TLR4/NF-κB/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4/NF-κB/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA.

Rosmanol induces breast cancer cells apoptosis by regulating PI3K/AKT and STAT3/JAK2 signaling pathways

Breast cancer is one of the most frequently diagnosed cancers amongst women; however, there is currently no effective treatment. Natural compounds are considered to contribute to cancer prevention and have a pivotal role in modulating apoptosis. Rosmanol is a phenolic diterpene compound with antioxidant and anti-inflammatory properties. In the present study, the effects of Rosmanol on breast cancer cell proliferation/apoptosis were investigated, and it was demonstrated that it inhibited the proliferation of MCF-7 and MDA-MB 231 cells but did not have a significant effect on normal human breast MCF-10A cells. In addition, the apoptotic process was accelerated by Rosmanol, through mitochondrial pathways and reactive oxygen species (ROS) production caused by DNA damage, which function further demonstrated by the attenuation and addition of the ROS inhibitor, N-acetyl-cysteine. It was also demonstrated that Rosmanol accelerated cell apoptosis, and arrested breast cancer cells in the S phase. Moreover, Rosmanol inhibited proliferation and promoted apoptosis of cancer cells via the inhibition of ERK and STAT3 signals, attributable to the increase in p-p38, the overexpression of protein inhibitor of activated STAT3, and the decrease in PI3K/AKT, ERK and JAK2/STAT3.

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

This review aimed to identify preclinical and clinical studies examining the effects of rosmarinic acid (RA), carnosic acid (CaA), rosmanol (RO), carnosol (CA), and ursolic acid (UA) against allergic and immunologic disorders. Various online databases, including PubMed, Science Direct, EMBASE, Web of Sciences, Cochrane trials, and Scopus, were searched from inception until October 2022. Due to the suppression of the nuclear factor-κB (NF-κB) pathway, the main factor in allergic asthma, RA may be a promising candidate for the treatment of asthma. The other ingredients comprising CA and UA reduce the expression of interleukin (IL)-4, IL-5, and IL-13 and improve airway inflammation. Rosemary's anti-cancer effect is mediated by several mechanisms, including DNA fragmentation, apoptosis induction, inhibition of astrocyte-upregulated gene-1 expression, and obstruction of cell cycle progression in the G1 phase. The compounds, essentially found in Rosemary essential oil, prevent smooth muscle contraction through its calcium antagonistic effects, inhibiting acetylcholine (ACH), histamine, and norepinephrine stimulation. Additionally, CA exhibits a substantially greater interaction with the nicotinic ACH receptor than a family of medications that relax the smooth muscles, making it a potent antispasmodic treatment. The components have demonstrated therapeutic effects on the immune, allergy, and respiratory disorders.

Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways

Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. In this study, we investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2. Treatment with rosmanol also reduced translocation of the nuclear factor-kappaB (NF-kappaB) subunits by prevention of the degradation and phosphorylation of inhibitor kappaB (IkappaB). Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB, signal transducer and activator of transcription-3 (STAT3), and the protein expression of C/EBPbeta and C/EBPdelta. We also found that rosmanol suppressed LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-kappaB and STAT3 through interfering with the activation of PI3K/Akt and MAPK signaling. Taken together, rosmanol might contribute to the potent anti-inflammatory effect of rosemary and may have potential to be developed into an effective anti-inflammatory agent.

Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells

Rosemary (Rosmarinus officinalis), a culinary spice and medicinal herb, has been widely used in European folk medicine to treat numerous ailments. Many studies have shown that rosemary extracts play important roles in anti-inflammation, anti-tumor, and anti-proliferation in various in vitro and in vivo settings. The roles of tumor suppression of rosemary have been attributed to the major components, including carnosic acid, carnosol, and rosmarinic acid, rosmanol, and ursolic acid. This study was to explore the effect of rosmanol on the growth of COLO 205 human colorectal adenocarcinoma cells and to delineate the underlying mechanisms. When treated with 50 μM of rosmanol for 24h, COLO 205 cells displayed a strong apoptosis-inducing response with a 51% apoptotic ratio (IC(50) ?42 μM). Rosmanol increased the expression of Fas and FasL, led to the cleavage and activation of pro-caspase-8 and Bid, and mobilized Bax from cytosol into mitochondria. The mutual activation between tBid and Bad decreased the mitochondrial membrane potential and released cytochrome c and apoptosis-inducing factor (AIF) to cytosol. In turn, cytochrome c induced the processing of pro-caspase-9 and pro-caspase-3, followed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). These results demonstrate that the rosmanol-induced apoptosis in COLO 205 cells is involvement of caspase activation and involving complicated regulation of both the mitochondrial apoptotic pathway and death receptor pathway.