Scutellaria moniliorrhiza Komarov Labiatae is a perennial he

Scutellaria moniliorrhiza Komarov (Labiatae) is a perennial herb and mainly distributed in Jilin province, China. In traditional Chinese medicine, the whole plants have been used to clear away heat-evil, expel superficial evils, eliminate stasis and reduce edema (He et al., 2012). In previous phytochemical studies, nineteen flavanoids were separated and some of them showed anti-inflammatory activities (Han et al., 2017). As part of our ongoing search for more biologically active flavanoids, a further separation of an ethanolic extract from S. moniliorrhiza was performed, and led to the isolation of four undescribed flavonoid alkaloids. Flavonoid alkaloids belong to a unique group of natural products. In almost all cases, these compounds contain a five- or six-membered nitrogen heterocycle which is connected to the A-ring of the flavonoid skeleton. Furthermore, almost all compounds in this class are found in plants which are used in folk medicine as herbal remedy for the treatment of a wide range of conditions (Khadem and Marles, 2012), and some of which were reported to possess valuable pharmacological activity. Research into the field of flavonoid alkaloids gained even more attention today (Jain et al., 2012, Khadem and Marles, 2012). Four undescribed flavonoid alkaloids (1–4) (Fig. 1), named as scumonilines A-D, respectively, were originally isolated as a racemate. With the help of chiral HPLC, they were successfully separated and prepared, and their chemical structures including absolute configuration were also elucidated on the basis of extensive spectroscopic analyses. In in vitro biological tests, these undescribed nitrogen-containing flavonoid were screened for the anti-inflammatory activity, with the inhibition rates of release of β-glucuronidase from polymorphonuclear NPI-0052 of rats being in the range 62.7%–63.6% at concentrations of 10 μM. Moreover, they showed inhibitory activity against aldose reductase, with IC50 values being in the range of 2.29–3.03 μM. Herein, we report on the isolation, structural elucidation, as well as the evaluation of bioactivities of four undescribed flavonoid alkaloids.
Results and discussion
Conclusions In summary, four undescribed flavonoid alkaloids, as two pairs of enantiomers, were separated and isolated from the whole plant of Scutellaria moniliorrhiza, and characterized mainly by NMR and CD spectroscopic techniques. The discovery of undescribed flavonoid alkaloids is a further demonstration to the diverse constituents from the genus Scutellaria, and their presence as markers may be helpful in chemotaxonomical classifications. Furthermore, the anti-inflammatory activities and inhibitory activity against aldose reductase of four undescribed flavonoid alkaloids were investigated. The results proved the four undescribed compounds possess anti-inflammatory activities close to that of the positive control, and inhibitory activities with IC50 values being in the range of 2.29–3.03 μM.
Experimental section
Acknowledgements This study was financially supported by the Natural Science Foundation of China (21372189) and Natural Science Foundation of Shandong Province (ZR2014HM080). The authors are grateful to Ms. Xiu-Li Yin, Li (Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences) for the measurements of FABMS, HR-FABMS, UV, IR, NMR and CD spectra, respectively. The authors also gratefully acknowledge Ms. Feng Zhao (School of Pharmaceutical Science, Yantai University) for the bioactivity screenings.
Introduction More than 50 years have passed since the hyperosmotic theory of the galactose-induced cataract linked to aldose reductase activity was first proposed [1]. At that time, it really looked like a short cut to finding tools to counteract diabetic complications. In fact, as formulated, the control of polyol formation through AR inhibition, appeared to be a logical intervention in secondary complications of diabetes. Besides the osmotic stress, other damaging events may be associated with an enhanced flux of the polyol pathway. These include a substantial alteration of the physiological ratios of the redox couples of both NAD and NADP, with a consequent decrease in antioxidant defense ability [2] and, finally, a potential increase in protein glycation phenomena due to an increase in fructose levels [3], [4], [5].