Erianin: A phytoestrogen with therapeutic potential.

Erianin, a phytoestrogen with therapeutic potential, is one of the major active components of Dendrobll caulis. Erianin has a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, anti-diabetic retinopathy, anti-psoriasis, and antibacterial effects. Especially, in regard to the anti-tumor effect of erianin, the underlying molecular mechanism has been partly clarified. In fact, the numerous pharmacological actions of erianin are complex and interrelated, mainly including ERK1/2, PI3K/Akt, JAK2/STAT3, HIF-1α/PD-L1, PPT1/mTOR, JNK/c-Jun, and p38 MAPK signal pathway. However, on account of the poor water solubility and the low bioavailability of erianin, greatly affected and limited its further development and application. And it is worthwhile and meaningful to explore more extensive pharmacological effects and mechanisms, clarify pharmacokinetics, and synthesize the derivatives of erianin. Conclusively, in this paper, the pharmacological effects of erianin and its mechanism, pharmacokinetics, and derivatives studies were reviewed, in order to provide a reference for the development and application of erianin.

[Research progress on mechanism of Carthamus tinctorius in ischemic stroke therapy].

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3ß(GSK3ß) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.

Pharmacological Activities of Safflower Yellow and Its Clinical Applications.

Background: Safflower is an annual herb used in traditional Chinese herbal medicine. It consists of the dried flowers of the Compositae plant safflower. It is found in the central inland areas of Asia and is widely cultivated throughout the country. Its resistance to cold weather and droughts and its tolerance and adaptability to salts and alkalis are strong. Safflower has the effect of activating blood circulation, dispersing blood stasis, and relieving pain. A natural pigment named safflower yellow (SY) can be extracted from safflower petals. Chemically, SY is a water-soluble flavonoid and the main active ingredient of safflower. The main chemical constituents, pharmacological properties, and clinical applications of SY are reviewed in this paper, thereby providing a reference for the use of safflower in preventing and treating human diseases. Methods: The literature published in recent years was reviewed, and the main chemical components of SY were identified based on chemical formula and structure. The pharmacological properties of hydroxysafflor yellow A (HSYA), SYA, SYB, and anhydrosafflor yellow B (AHSYB) were reviewed. Results: The main chemical constituents of SY included HSYA, SYA, SYB, and AHSYB. These ingredients have a wide range of pharmacological activities. SY has protective effects on the heart, kidneys, liver, nerves, lungs, and brain. Moreover, its effects include, but are not limited to, improving cardiovascular and cerebrovascular diseases, abirritation, regulating lipids, and treating cancer and diabetic complications. HSYA is widely recognised as an effective ingredient to treat cardiovascular and cerebrovascular diseases. Conclusion: SY has a wide range of pharmacological activities, among which improving cardiovascular and cerebrovascular diseases are the most significant.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review.

Cancer is still an insurmountable problem for humans and critically attacking human health. In recent years, natural products have gained increasing attention in the field of anti-tumor due to their extensive sources and minimal side effects. Maslinic acid (MA), a pentacyclic triterpene acid mainly derived from the olive tree (Olea europaea L.) has been confirmed to possess great anti-cancer effects. This paper reviewed the inhibitory effect of MA and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others. MA inhibited the proliferation of various tumor cells and showed lower IC50 values in melanoma 518A2 cells and gastric cancer MKN28 cells compared with other cell lines. A series of semi-synthetic derivatives obtained by modifying MA chemical structure have been shown to have high cytotoxicity to human tumor cell lines, but low cytotoxicity to non-malignant cells, which is conducive to developing its potential as a chemotherapeutic agent. These studies suggest that MA derivatives have broad prospects in the development of antitumor therapeutics in the future and warrant further study.

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

Water-soluble alkaloids extracted from Aconiti Radix lateralis praeparata protect against chronic heart failure in rats via a calcium signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics. METHODS: Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure. RESULTS: AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and ß-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a. CONCLUSIONS: AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.