Loganin CAS NO.18524-94-2

Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells.[Pubmed: 21241762]

Neurochem Int. 2011 Mar;58(4):533-41

METHODS AND RESULTS:
We investigated the mechanisms underlying the protective effects of Loganin against hydrogen peroxide (H(2)O(2))-induced neuronal toxicity in SH-SY5Y cells. The neuroprotective effect of Loganin was investigated by treating SH-SY5Y cells with H(2)O(2) and then measuring the reduction in H(2)O(2)-induced apoptosis using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. Following H(2)O(2) exposure, Hoechst 33258 staining indicated nuclear condensation in a large proportion of SH-SY5Y cells, along with an increase in reactive oxygen species (ROS) production and an intracellular decrease in mitochondria membrane potential (MMP). Loganin was effective in attenuating all the above-stated phenotypes induced by H(2)O(2). Pretreatment with Loganin significantly increased cell viability, reduced H(2)O(2)-induced LDH release and ROS production, and effectively increased intracellular MMP. Pretreatment with Loganin also significantly decreased the nuclear condensation induced by H(2)O(2). Western blot data revealed that Loganin inhibited the H(2)O(2)-induced up-regulation of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, increased the H(2)O(2)-induced decrease in the Bcl-2/Bax ratio, and attenuated the H(2)O(2)-induced release of cytochrome c from mitochondria to the cytosol. Furthermore, pretreatment with Loganin significantly attenuated the H(2)O(2)-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2).
CONCLUSIONS:
These results suggest that the protective effects of Loganin against H(2)O(2)-induced apoptosis may be due to a decrease in the Bcl-2/Bax ratio expression due to the inhibition of the phosphorylation of JNK, p38, and ERK 1/2 MAPKs. Loganin's neuroprotective properties indicate that this compound may be a potential therapeutic agent for the treatment of neurodegenerative diseases.

Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products.[Pubmed: 25623853]

Life Sci. 2015 Feb 15;123:78-85.

Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of Loganin on diabetic nephropathy in vivo.
METHODS AND RESULTS:
We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, Loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, Loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that Loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney.
CONCLUSIONS:
Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy.

Loganin improves learning and memory impairments induced by scopolamine in mice.[Pubmed: 19666019 ]

Eur J Pharmacol. 2009 Oct 1;619(1-3):44-9.

Loganin is an iridoid glycoside found in the Flos lonicerae, Fruit cornus, and Strychonos nux vomica.
METHODS AND RESULTS:
We investigated the effect of Loganin on learning and memory impairments induced by scopolamine (0.5mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and the Morris water maze tests in mice. In the Y-maze test, Loganin (40 mg/kg, p.o.) significantly improved the scopolamine-induced memory impairment. In addition, Loganin (20 and 40 mg/kg, p.o.) significantly reversed scopolamine-induced impairments measured by the passive avoidance and the Morris water maze tests. A day after the last trial session of the Morris water maze test (probe trial session), Loganin (20 and 40 mg/kg) dose-dependently increased the latency time in the target quadrant. Furthermore, Loganin significantly inhibited acetylcholinesterase activity in the hippocampus and frontal cortex.
CONCLUSIONS:
Loganin may have anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in Alzheimer's disease.

Kinetic and molecular docking studies of loganin and 7-O-galloyl-D-sedoheptulose from Corni Fructus as therapeutic agents for diabetic complications through inhibition of aldose reductase.[Pubmed: 25315636]

Neuroprotective effect of loganin against Aβ25-35-induced injury via the NF-κB-dependent signaling pathway in PC12 cells.[Pubmed: 25778782]

Food Funct. 2015 Apr 8;6(4):1108-16.

Amyloid-beta (Aβ) protein, the main constituent of senile plaques, is believed to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). AD is closely associated with inflammatory reactions which are considered to be responses to Aβ deposition.
METHODS AND RESULTS:
The present study investigated the effect of Loganin on Aβ25-35-induced inflammatory damage and the underlying molecular mechanism of its neuroprotective action. Loganin predominantly prevented Aβ25-35-stimulated cell death through suppressing ROS generation, and attenuating apoptosis by inhibiting caspase-3 activity and regulating cell cycle. Furthermore, Loganin suppressed the level of TNF-α and protein expression of iNOS and COX-2 in Aβ25-35-injured PC12 cells. These inhibitions appeared to correlate with the suppression of NF-κB activation by Loganin, as pre-treating cells with Loganin blocked the translocation of NF-κB into the nuclear compartment and degradation of the inhibitory subunit IκB. Loganin substantially inhibited phosphorylation of MAPKs including ERK1/2, p38 and JNK, which are closely related to regulation of NF-κB activation.
CONCLUSIONS:
Taken together, the results implied that Loganin attenuated neuroinflammatory responses through the inactivation of NF-κB by NF-κB dependent inflammatory pathways and phosphorylation of MAPK in Aβ25-35-induced PC12 cells.

Arch Pharm Res. 2015 Jun;38(6):1090-8.

Aldose reductase (AR) is a key enzyme in the polyol pathway that is strongly implicated in the pathogenesis of diabetic complications. AR inhibitors have been proposed as therapeutic agents for diabetic complications through suppression of sorbitol formation and accumulation.
METHODS AND RESULTS:
In this study, we evaluated whether two major compounds of Corni Fructus, Loganin and 7-O-galloyl-D-sedoheptulose, had an inhibitory effect on diabetic complications through AR inhibition. Because the iridoid glycoside Loganin and the low-molecular-weight polyphenol 7-O-galloyl-D-sedoheptulose showed marginal inhibitory activities against rat lens AR (RLAR) and human recombinant AR (HRAR) in inhibition assays, we performed enzyme kinetic analyses and molecular simulation of the interaction of these two compounds with AR to further investigate their potential as inhibitors of diabetic complications. In kinetic analysis using Lineweaver-Burk plots and Dixon plots, Loganin and 7-O-galloyl-D-sedoheptulose were both mixed inhibitors of RLAR with inhibition constants (K i) of 27.99 and 128.68 μΜ, respectively. Moreover, molecular docking simulation of both compounds demonstrated negative binding energies (Autodock 4.0 = -6.7; -7.5 kcal/mol; Fred 2.0 = -59.4; -63.2 kcal/mol) indicating a high affinity and tight binding capacity for the active site of the enzyme. Iridoid nucleus and aromatic ring systems and glycoside and sedoheptulose moieties were found to bind tightly to the specificity pocket and the anion binding pocket in RLAR through Phe123, His111, Trp21, Tyr49, His111, and Trp112 residues.
CONCLUSIONS:
Our results clearly indicate that Loganin and 7-O-galloyl-D-sedoheptulose have great promise for the treatment of diabetic complications through inhibition of AR.

Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal glucolipotoxicity and inflammation in type 2 diabetic db/db mice.[Pubmed: 20826139 ]

Eur J Pharmacol. 2010 Dec 1;648(1-3):179-87.

Previously, we have reported that Corni Fructus possessed hypoglycemic and hypocholesterolemic effects in streptozotocin-induced type 1 diabetic rats and diet-induced hypercholesterolemic rats.
METHODS AND RESULTS:
Herein, we have focused on the effect and mechanism of Loganin, a major iridoid glycoside of Corni Fructus, on the type 2 diabetic db/db mice. Loganin was orally administered to db/db mice at a dose of 20 or 100 mg/kg body weight daily for 8 weeks. The biochemical factors and expressions of protein and mRNA related to lipid metabolism, inflammation, advanced glycation endproducts, and its receptor were measured. In Loganin-treated db/db mice, hyperglycemia and dyslipidemia were ameliorated in both the serum and hepatic tissue; however, in the kidney, only triglyceride was reduced. The enhanced oxidative stress was alleviated by Loganin through a decrease in thiobarbituric acid-reactive substances (liver and kidney) and reactive oxygen species (serum, liver, and kidney), as well as augmentation of the oxidized to reduced glutathione ratio (liver and kidney). The marked lipid-regulatory effect of Loganin was exerted in the liver of type 2 diabetic mice via suppressing mRNA expressions related to lipid synthesis and adjusting the abnormal expression of peroxisome proliferator-activated receptor α and sterol regulatory-element binding protein in the nucleus. Furthermore, Loganin inhibited advanced glycation endproduct formation and the expression of its receptor, and nuclear factor-kappa B-induced inflammation in the hepatic tissue of db/db mice.
CONCLUSIONS:
Loganin exhibits protective effects against hepatic injury and other diabetic complications associated with abnormal metabolic states and inflammation caused by oxidative stress and advanced glycation endproduct formation.