Among the isolated constituents, Sennoside A and B were effective on both RDDP and RNase H RT-associated functions in biochemical assays.
Conclusion: Sennoside A is a new scaffold for the development of HIV-1 dual RT inhibitors.
Among the anthraquinones reported to be present in Rhubarb (Ye et al., 2007), Sennosides (Sennoside A and Sennoside B) are considered to be the purgative components (Xiao et al., 1980; Zwaving, 1972), Rhein and Physcion possess antitumor and anti-inflammatory properties (Zwaving, 1972; He et al., 2011), with the latter presenting also hepatoprotective, antifungal and anticancer activities (He et al., 2011).
The reference compounds AloeEmodin, Rhein, Emodin, Chrysophanol, Physcion were purchased from the National Institute for Control of Pharmaceuticals and Biological Products (Beijing, China), and Sennoside A and Sennoside B from the Mansite Pharmaceutical Co.
Efavirenz at 0.1 [micro]M, Sennoside A at 20 [micro]M, Sennoside B at 20 [micro]M and RDS1760 at 25 [micro]M).
Raltegravir was used at 1 [micro]M, Efavirenz at 1.5 [micro]M, Zidovudine at 0.4 [micro]M, and Sennoside A at 250 [micro]M.
Specifically, these components included anthraquinone derivatives such as Emodin, Crysophanol, Aloe-Emodin, Physcion, Rhein and Sennoside (both Sennoside A and Sennoside B).
Evaluation of the effects of Sennoside A and B on mutated RT
Thus, we firstly tested the effect of Sennoside A and B on three known single RT mutants involved in NNRTI resistance such as K103N, Y181C and Y188L RTs, using Efavirenz as positive control (Table 3).
2 shows the transport characteristics of sennoside A and sennidine A as examples).
[P.sub.c] values for sennoside A and B ranged from 2.6 X [10.sup.-7] to 5.2 x [10.sup.-7] cm/s in apical to basolateral direction, and 2.2 x 10.sup.-7] to 14.4 X [10.sup.-7] in basolateral to apical direction, respectively.
When transport rates were monitored in the secretory (basolateral to apical) direction, comparatively higher permeability coefficients and % transport were observed (except for sennoside A at 100 [micro]M; Table 1).