Comparison of the chemical constituents and anti-Alzheimer's disease effects of Uncaria rhynchophylla and Uncaria tomentosa

Abstract

Background: Uncaria tomentosa, which has similar chemical constituents with Uncaria rhynchophylla, has been reported to alleviate cognitive impairments in Alzheimer's disease (AD) animal models. This study aimed to compare the chemical constituents and anti-AD effect of the ethanol extracts of U. tomentosa (UTE) and U. rhynchophylla (URE).

Methods: The high-performance liquid chromatography (HPLC) was used to compare the chemical constituents of UTE and URE. Streptozotocin (STZ) was intracerebroventricularly (ICV) injected into adult male Sprague-Dawley (SD) rats to establish AD model. UTE (400 mg/kg) or URE (400 mg/kg) was administrated intragastrically once daily to the rats for 6 consecutive weeks. Morris water maze (MWM) test was conducted to assess the neurological functions in the STZ-induced AD rats. The brain tissues of the rats were harvested for further biochemical assay.

Results: The MWM test results showed both UTE and URE could significantly improve the learning and memory impairments induced by STZ in rats. Both UTE and URE could significantly inhibit the hyperphosphorylation of tau protein, reduce the elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), enhance activities of antioxidant enzymes (SOD, CAT and GPx) and increase the protein expression of HO-1. In addition, UTE could decrease the malondialdehyde (MDA) level. Furthermore, both UTE and URE significantly enhanced Akt activation, down regulated the activation of glycogen synthase kinase 3β (GSK-3β), and induced the nuclear translocation of Nrf2 in the STZ-induced AD rats.

Conclusions: UTE and URE contained similar chemical constituents. We found for the first time that both of them could ameliorate cognitive deficits in the STZ-induced AD rats. The underlying molecular mechanism involve suppression of tau hyperphosphorylation, anti-oxidant and anti-neuroinflammation via modulating Akt (Ser473)/GSK3β (Ser9)-mediated Nrf2 activation. These findings amply implicate that both of UTE and URE are worthy of being developed clinically into pharmaceutical treatment for AD.

Keywords: Akt/GSK3β/Nrf2 pathway; Alzheimer’s disease; Rats; Streptozotocin; Uncaria rhynchophylla; Uncaria tomentosa.

Fig. 1

High-performance liquid chromatography profiles of 70% aqueous ethanol extracts of Uncaria tomentosa (UTE) and Uncaria rhynchophylla (URE). 1: isorhynchophylline; 2: corynoxeine; 3: rhynchophylline; 4: isocorynoxeine

Fig. 2

Effects of UTE and URE on the cognitive impairments in the STZ-induced AD rat model assessed by Morris Water Maze test (n = 9–10). A Representative images of the swimming path; B escape latency to platform during training days; C the number of target quadrant crossing in the probe tests; D swimming speed; E the time spent in the target quadrant in the probe test. Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. *p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 3

Effects of UTE and URE on tau hyperphosphorylation on the STZ-induced AD rat model (n = 5). Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. *p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 4

Effects of UTE and URE on pro-inflammatory cytokines in the STZ-induced AD rat model (n = 5). Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. *p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 5

Effects of UTE and URE on oxidative stress in the STZ-induced AD rat model (n = 5). A SOD activity; B CAT activity; C GPx activity; D MDA level; E The protein expression of HO-1. Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. *p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 6

Effects of UTE and URE on the activated Nrf2 signaling in the STZ-induced AD rat model (n = 4–5). A The protein expressions of nuclear Nrf2, cytosolic Nrf2, total Nrf2 and Keap1; B Quantitative analysis for the western blot results. Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. * p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 7

Effects of UTE and URE on Akt/GSK3β pathway in the STZ-induced AD rat model (n = 4–5). A The protein expressions of p-Akt (S473), Akt, p-GSK-3β (S9), and GSK-3β; B Quantitative analysis for the western blot results. Data were expressed as the mean ± SEM. ^#p < 0.05 and ^##p < 0.01 compared with the sham control group. *p < 0.05 and **p < 0.01 compared with the STZ control group

Fig. 8

The schematic drawing summarizing the proposed mechanisms for the anti-neuroinflammatory and antioxidant effects of UTE and URE in the STZ-induced AD rat model. The mechanisms involve the inhibition of hyperphosphorylated tau protein, the promotion of antioxidant enzymes expression, the reduction of pro-inflammatory cytokines and the role of Akt (Ser473)/GSK3β (Ser9)-mediated Nrf2 activation