Strictosamide

Chem Biol Drug Des. 2015 Oct;86(4):523-30.

Synthesis and Biological Evaluation of Strictosamide Derivatives with Improved Antiviral and Antiproliferative Activities.[Pubmed: 25589048]

A series of novel derivatives of Strictosamide were synthesized and biologically evaluated.
METHODS AND RESULTS:
Most of the new compounds exhibited improved activities than the parent compound Strictosamide. Among them, compounds Ib and If possessed antiviral activities against influenza A virus (A/Jinan/15/90) with IC50 values of 4.12 and 12.35 μg/mL, respectively. Compound Ie possessed antiviral activity against respiratory syncytial virus (RSV) with an IC50 value of 9.58 μg/mL.
CONCLUSIONS:
Both compounds IIc and IId had moderate antiproliferative effects against five human cancer cell lines. The preliminary structure-activity relationships were also concluded. This study provides a promising new template with potential antiviral activity.

Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2014(7):1558-64.

Experimental Research on Effect of Strictosamide Injection on Cardiovascular System.[Reference: WebLink]

This study was aimed to investigate the effects of high-dose Strictosamide injection on cardiovascular system of anesthetized beagle dogs and to examine the inhibition of Strictosamide on ion channels in vitro.
METHODS AND RESULTS:
Indexes such as changes of systolic blood pressure(Sys), diastolic blood pressure(Dia), mean blood pressure(MBP), heart rate(HR), PR, QRS, QT, QTcb and QTcv at different time points before and after Strictosamide injection in dogs were monitored by the polygraph system. The inhibition of Strictosamide at different concentrations on hERG potassium channel in CHO-hERG cells and Nav1.5 sodium channel in HEK-293-Nav1.5 cells were measured by whole-cell patch-clamp method. The results showed that compared with the blank control group, Sys, Dia, MBP and HR were obviously declined 15 min after medication in the Strictosamide(60, 18 mg·kg-1) group and the vehicle-control group(containing tween-80)(P 0.05). After medication, all indexes were recovered. Compared to the vehicle-control group, there were no significant differences at different time points in each medication groups. Compared with the blank control group and before medication, the QT interval, QTcb and QTcv were significantly prolonged 15 min after medication in the Strictosamide(60, 18, 6 mg·kg-1) group and the vehicle-control group(P 0.05). When medication stopped, indexes were recovered at certain level. Compared with the vehicle-control group, there were no significant differences of QT interval, QTcb and QTcv of each medication group at different time points(P 0.05). The inhibition of Strictosamide on hERG potassium channel and Nav1.5 sodium channel were weak with IC50 values of560.8 μM and 900 μM, respectively, which were far greater than the positive controls.
CONCLUSIONS:
It was concluded that single, high-dose intravenous injection of Strictosamide may lead to a lower blood pressure, a slower heart rate and a prolongation on the QT interval in beagle dogs, which returned to basal levels when medication stopped. It was speculated that the reduction of blood pressure and the slowing of heart rate were related to tween-80 contained in the vehicle control group. No significant inhibitory effects were detected on hERG potassium channel and Nav1.5 sodium channel in vitro, which suggested that other mechanisms may be involved in Strictosamide-induced QT interval prolongation in animals.

J Ethnopharmacol. 2009 Jan 12;121(1):117-22.

Effects of strictosamide on mouse brain and kidney Na+, K+-ATPase and Mg2+-ATPase activities.[Pubmed: 18992802]

Present study reports on the general bioactivity of Strictosamide and on its effects on Na(+),K(+)-ATPase and Mg(2+)-ATPase activities of Charles River male mouse. Strictosamide is the main glycoalkaloid of Sarcocephalus latifolius (Rubiaceae) leaves and roots, used as medicinal plant in folk medicine.
METHODS AND RESULTS:
In this work, we studied the in vitro effects of various concentrations of Strictosamide (0.25, 0.5, 1 or 2 mg/mL) and the in vivo effects of single doses (50, 100 or 200 mg/kg, i.p.) of this compound on kidney and brain Na(+),K(+)-ATPase and Mg(2+)-ATPase activities. Results of general study showed that Strictosamide is slightly toxic to Charles River mouse (LD(50)=723.17 mg/kg), producing CNS depression and kidney toxicity, but the exact mechanism of these effects could not be defined.
METHODS AND RESULTS:
Strictosamide inhibited the in vitro and in vivo Mg(2+)-ATPase activity on kidney but had nonsignificant effect on brain. Furthermore, Strictosamide had nonsignificant in vitro and in vivo effect on kidney Na(+),K(+)-ATPase activity but produced an in vivo increase of Na(+),K(+)-ATPase activity of brain, these findings suggesting that strictosamine may be related to the induction of alpha(2) isoform of Na(+),K(+)-ATPase and may account for the folk use of Sarcocephalus latifolius root infusion on hypertension.

Pharm Biol. 2014 Nov;52(11):1445-50.

In vivo anti-inflammatory and analgesic activities of strictosamide from Nauclea officinalis.[Pubmed: 25026342]

Strictosamide is the main representative constituent of Nauclea officinalis Pierre ex Pitard (Rubiaceae), which has been used for a long time in China to treat diseases related to infection and inflammation, but its pharmacological activities are not well studied.
METHODS AND RESULTS:
This work evaluates the anti-inflammatory and analgesic activities of Strictosamide by in vivo experiments. At 20 and 40 mg/kg, Strictosamide obviously decreased the TPA-induced mice ear edema (24.7 and 28.1% inhibition, respectively), and significantly inhibited acetic acid-stimulated peritoneal vascular permeability in mice (23.3 and 33.4% inhibition, respectively). It also significantly decreased the leukocytes in the mice peritoneal cavity induced by CMC-Na at all the tested doses (46.0, 49.1, and 58.7% inhibition, respectively). To acetic acid-induced writhing test in mice, Strictosamide markedly prolonged the pain latency at 20 and 40 mg/kg and decreased the writhing counts at 40 mg/kg (49.7% inhibition). However, it did not obviously improve the pain threshold of mice in hot-plate test.
CONCLUSIONS:
Strictosamide may have important effects on inflammation and inflammatory pain. The results provide scientific support for the role of Strictosamide in the use of N. officinalis to treat inflammatory diseases.

Chinese Journal of Experimental Traditional Medical Formulae,2012,18(15):170-4.

Antibacterial and Antiviral Effects of Strictosamide.[Reference: WebLink]

To observe the antibacterial and antiviral activities,and provide certain experimental data for Strictosamide that is intended for upper respiratory tract infection.
METHODS AND RESULTS:
The in vitro antibacterial activities on standard staphylococcus aureus and other 9 strains were observed by both test-tube and plating methods,and the protective effects on mice infected by staphylococcus aureus and streptococcus pneumonia were also observed.Mice were divided into 5 groups,such as normal group,model group,reduning group(crude drugs 8.7 g·kg-1),low and high dosage(20,40 mg·kg-1) of Strictosamide groups.They were injected intraperitoneally once a day for 7 days.At 1 h after the last injection,staphylococcus aureus or streptococcus pneumonia was injected intraperitoneally to mice,and then the death of mice was observed within 7 days.The in vitro antiviral activities were observed on the model of MDCK cells infected by influenza A(A/PR8/34(H1N1)) and B(B/Jingfang 98-76) virus,and the in vivo antiviral activities were observed by the model of mice infected by influenza A virus.Mice were divided into 5 groups,such as normal group,model group,reduning group(crude drugs 8.7 g·kg-1),low and high dosage(20,40 mg·kg-1) of Strictosamide groups.They were injected intraperitoneally once a day for 5 days,and virus was given to mice by nose on the first day.After the last injection,the lung lesions and pathological changes were observed,and the pulmonary index was also calculated. Strictosamide had inhibiting effects on standard escherichia coli and other 6 strains in vitro with MIC of 5 g·L-1.At 10 g·L-1,the diameters of inhibiting bacteria circle of diplococcus pneumonia and other 4 strains were 13-25 mm.At 40 mg·kg-1,the survival rate of mice infected by staphylococcus aureus and streptococcus pneumonia was 70% and 55%,separately.Strictosamide showed inhibitory effects on both influenza A and B viruses in vitro with IC50 values of 0.649,0.323 g·L-1,respectively.It also significantly inhibited increased pulmonary index and improved pulmonary pathological lesions of the infected mice caused by influenza A virus,and the inhibitory rate of pulmonary index was 39.8% at 40 mg·kg-1.
CONCLUSIONS:
Strictosamide possesses antibacterial and antiviral activities.