Therapeutic and medicinal effects of snowdrop (Galanthus spp.) in Alzheimer's disease: A review.

Genus Galanthus (Amaryllidaceae) is an early spring flowering bulbous plant. Galanthus species contain alkaloids that have shown pharmacological activity. Galanthamine is an alkaloid that was extracted from Galanthus and other Amaryllidaceae. Owing to its acetylcholinesterase (AChE) inhibitory activity, galanthamine is used and marketed to treat Alzheimer's disease (AD). The aim of the present study, while introducing the botanical and pharmacological characteristics and various aspects of the medicinal plant Galanthus, is to emphasize the effect of this plant in the treatment of AD. In this web-based study in 2021, articles indexed in scientific databases in English language, including ISI Web of Knowledge, PubMed, Scopus, MedLib, Medknow, SID, ISC, and also articles and e-books published in Springer, Elsevier, John Wiley and Sons, and Taylor and Francis were evaluated from 1990 to 2021, using the following keywords: "Galanthus" "galanthamine," "Alzheimer's disease." Amaryllidaceae-type alkaloids possess an anticholinesterase activity. The most studied Galanthus alkaloid, galanthamine, is a long-acting, selective, reversible, competitive inhibitor of AChE and an allosteric modulator of the neuronal nicotinic receptor for acetylcholine (ACh). Owing to its AChE inhibitory activity, galanthamine is used to treat certain stages of AD. Galantamine can act as a parasympathomimetic agent, especially as a reversible cholinesterase inhibitor. Galantamine is not structurally associated with other AChE inhibitors. Hence, its proposed mechanism of action involves the reversible inhibition of AChE, preventing hydrolysis of ACh that results in an increased concentration of ACh at cholinergic synapses.

Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines.

BACKGROUND: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. METHODS: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn's disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. RESULTS: Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. CONCLUSIONS: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.

Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells.

IRE1α endonuclease is a key regulator of endoplasmic reticulum (ER) stress that controls cell survival/apoptosis in cancers. Inhibition of IRE1α endonuclease leads to decreased splice XBP1 which decreases cell proliferation and increases cell death in cancer cells. Therefore, this study investigated the effects and mechanism of STF-083010 (an IRE1α inhibitor) on the cell growth/apoptosis of ovarian malignant cells via the XBP1-CHOP-Bim pathway following the induction of ER stress (ERS). ERS in OVCAR3 and SKOV3 cells was measured using Thioflavin T staining. The expression of ER stress response genes was evaluated by QRT-PCR. The levels of XBP1(s), PERK, phospho-PERK, p-PP2A, ATF4, BIP/GRP78, CHOP, and Bim proteins were evaluated using western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were assessed using BrdU, MTT, Annexin V-FITC/PI staining, and caspases-12 and -3 activity assays. The results showed increased XBP1, CHOP, and ATF-4 mRNA expression levels as well as high protein aggregation in STF-083010 and Tm co-treated cells. The IRE1α inhibitor down-regulated sXBP1 and BIP proteins, while XBP-1, p-PERK, ATF-4, CHOP, and Bim proteins were up-regulated. STF-083010 reduced cell proliferation and induced apoptosis through the activation of caspases-12 and -3 and Bax/Bcl-2 protein expression. In summary, the present data revealed the effects of STF-083010 in ER stress and apoptosis as well as signaling via XBP1/CHOP/Bim mediators. Thus, STF-083010 is proposed as a new target for the control of ERS in ovarian cancer cells.