Product name: Sennoside A
Synonym name:
Catalogue No.: BP1292
Cas No.: 81-27-6
Formula: C₄₂H₃₈O₂₀
Mol Weight: 862.746
Botanical Source: Sennae Folium
Physical Description:
Type of Compound: Anthraquinones

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Sennoside A, a kind of irritant laxative isolated from rhei rhizome, causes purgative actions in the intestine, it and Sennoside B have protective effects on gastric lesion. Sennoside A also is a new dual HIV-1 inhibitor effective on HIV-1 replication.

References:

Phytomedicine. 2016 Nov 15;23(12):1383-1391.    

Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication.    

Despite the availability of effective antiretroviral therapies, drugs for HIV-1 treatment with new mode of action are still needed. An innovative approach is aimed to identify dual HIV-1 inhibitors, small molecules that can inhibit two viral functions at the same time. Rhubarb, originated from Rheum palmatum L. and Rheum officinale Baill., is one of the earliest and most commonly used medicinal plants in Traditional Chinese Medicine (TCM) practice. We wanted to explore TCM for the identification of new chemical scaffolds with dual action abilities against HIV-1. 

METHODS AND RESULTS:

R. palmatum L. and R. officinale Baill. extracts along with their main single isolated constituents anthraquinone derivatives were tested on both HIV-1 Reverse Transcriptase (RT)-associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H) activities in biochemical assays. Active compounds were then assayed for their effects on HIV-1 mutated RTs, integrase (IN) and viral replication. Both R. palmatum L. and R. officinale Baill. extracts inhibited the HIV-1 RT-associated RNase H activity. Among the isolated constituents, Sennoside A and B were effective on both RDDP and RNase H RT-associated functions in biochemical assays. Sennoside A was less potent when tested on K103N, Y181C, Y188L, N474A and Q475A mutated RTs, suggesting the involvement of two RT binding sites for its antiviral activity. Sennoside A affected also HIV-1 IN activity in vitro and HIV-1 replication in cell-based assays. Viral DNA production and time of addition studies showed that Sennoside A targets the HIV-1 reverse transcription process. 

CONCLUSIONS:

Sennoside A is a new scaffold for the development of HIV-1 dual RT inhibitors.    

Biol Pharm Bull. 2011;34(9):1438-42.    

The influence of glycyrrhiza and antibiotics on the purgative action of sennoside a from Daiokanzoto in mice.    

Daiokanzoto (DKT), a Kampo medicine that includes the combination of two crude drugs (rhubarb and glycyrrhiza), is clinically effective for constipation. The aim of this study is to clarify the influence of glycyrrhiza, three glycyrrhiza constituents (glycyrrhizin, liquiritin, and liquiritin apioside), and eight antibiotics on the purgative action of DKT, rhubarb, or Sennoside A, a constituent of rhubarb, in mice. 

METHODS AND RESULTS:

The purgative actions of rhubarb and Sennoside A were significantly intensified when glycyrrhiza was co-administered orally to mice. Liquiritin and liquiritin apioside but not glycyrrhizin showed significant amplification of the purgative action in a dose-dependent manner. The purgative actions of DKT and Sennoside A were significantly reduced by the pre-administration of ampicillin, cefcapene pivoxil, faropenem, fosfomycin, or kanamycin, but were not affected by the pre-administration of clarithromycin or levofloxacin. On the other hand, the purgative action of Sennoside Awas significantly reduced by the pre-administration of minocycline, whereas that of DKT was not affected. The effect of minocycline on the purgative action of Sennoside A was lost when glycyrrhiza was co-administered. 

CONCLUSIONS:

These results suggest that liquiritin and liquiritin apioside contribute as active substances for the purgative action of DKT, and some antibiotics reduce the purgative action of DKT and Sennoside A. Furthermore, glycyrrhiza has the ability to recover the purgative action of Sennoside A suppressed by minocycline via an unknown mechanism.    

The FASEB Journal, 2015, 29(1): 716.10.    

Protective mechanism on gastric lesion of Sennoside A and Sennoside B   

Sennoside A and sennoside B is evacuant to increase the sensitivity of the colon. 

METHODS AND RESULTS:

In vivo test, we performed HCl·ethanol-induced gastritis test, indomethacin-induced gastric ulcer test, gastric secretion in pylorus-ligated test, H+/K+ATPase activity test, gastric emptying and intestinal motility test. In vitro test, we examined acid-neutralizing capacity, quantity of PGE2 and inhibition of H. pylori colonization and we confirmed apoptosis using DAPI nuclear staining, FACS analysis. Sennoside A and B inhibit lesion index in gastritis and gastric ulcer in rats. These results showed that these components reduced gastric juice, an aggressive factor and total acidity and increased pH moderately. In addition, it was made sure that proton pump inhibiton influenced on gastric acid secretion control and that colonization inhibiting activity on H. pylori. 

CONCLUSIONS:

As protection enhancing factors to gastric damage, Sennoside A and B increased PGE2 in a concentration-dependent manner.    

HPLC of Sennoside A

NMR of Sennoside A

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Sennoside A (CAS number: 81-27-6) is an important class of natural anthraquinone glycoside compounds, mainly found in the leaves of Cassia angustifolia. As an important component in traditional Chinese medicine and herbal laxatives, senna glycoside A is widely used for treating constipation due to its significant laxative effect. Moreover, recent studies have shown that senna glycoside A exhibits unique pharmacological activity in the antiviral field, especially in inhibiting HIV-1 infection, making it one of the hotspots in natural product pharmacology research. This paper systematically reviews the chemical structure and physicochemical properties of senna glycoside A, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and conducts an in-depth discussion in conjunction with its clinical application prospects, aiming to provide theoretical basis and research guidance for the development and utilization of this natural product.

Chemical structure and physicochemical properties

Senna glycoside A is an anthraquinone glycoside with the molecular formula C42H38O20 and a molecular weight of 862.7460. Its structure consists of two anthraquinone units connected by glycosidic bonds to form a dimer, featuring a typical anthraquinone framework and multiple hydroxyl and glycosyl modifications. The LogP value of senna glycoside A is 0.8253, indicating strong hydrophilicity, and the TPSA (Topological Polar Surface Area) reaches 347.96, reflecting its high polarity. Its water solubility is 0.7073, indicating a certain solubility in water. Its low blood-brain barrier permeability suggests difficulty entering the central nervous system, reducing the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity; Ames mutagenicity test was zero, indicating a low genotoxicity risk. Overall, the physicochemical properties of senna glycoside A align with the typical characteristics of natural products and provide a solid safety foundation.

Plant Origins and Extraction Methods

Senna glycoside A is mainly found in the leaves of the leguminous plant Cassia angustifolia and its related species. Senna leaves are a traditional Chinese medicinal herb, widely distributed in India, Africa, and parts of Asia. Its leaves are rich in anthraquinone substances, with senna glycosides A and senna B being the main active ingredients.

The extraction method typically uses water extraction or alcohol extraction combined with liquid-liquid separation technology. The common process is: first, the dried senna leaves are crushed, then extracted with hot water or 70% ethanol. The extract is filtered and concentrated, then extracted separately using organic solvents such as ethyl acetate and chloroform. Further column chromatography (such as silica gel columns and C18 reversed phase columns) is used to purify high-purity senna glycoside A. In recent years, the application of new technologies such as ultrasound-assisted extraction and microwave-assisted extraction has improved extraction efficiency and purity. In addition, high-performance liquid chromatography (HPLC) and mass spectrometry techniques are widely used for qualitative and quantitative analysis of senna glycoside A to ensure quality control of extracts.

Pharmacological activity research

Laxative effect

Senna glycoside A, as the main active ingredient in senna leaves, has a significant laxative effect. Its laxative effect mainly works by stimulating intestinal peristalsis and promoting intestinal juice secretion. In vivo and in vitro experiments show that senna glycoside A can increase the frequency and amplitude of contraction in the smooth muscle of the colon, accelerating the advancement of intestinal contents. At the same time, senna glycoside A regulates ion channels and aquaporins in intestinal epithelial cells, promotes water penetration into the intestinal lumen, softens stool, and relieves constipation symptoms.

Anti-HIV-1 activity

Recent studies have found that senna glycoside A has the potential to inhibit HIV-1 replication. In vitro experiments showed that senna glycoside A significantly inhibited HIV-1 reverse transcriptase (RT)-associated DNA polymerase (RDDP) and RNase H, with IC50s of 1.9 μM and 5.3 μM, respectively. Additionally, the IC50 inhibition of the overall HIV-1 replication process of Senna glycoside A was 3.8 μM, indicating its potential as an HIV-1 reverse transcriptase inhibitor. This activity provides a new research direction for senna glycoside A in the development of antiviral drugs.

Other pharmacological effects

Some studies have also reported potential activities such as antioxidant, anti-inflammatory, and antitumor effects of senna glycoside A, but the related mechanisms have not been fully elucidated and require further systematic research.

Mechanism of action and molecular targets

Mechanism for promoting bowel movements

The laxative effect of senna glycoside A is mainly achieved through multi-target coordinated regulation. Its targets include:

• CFTR (Cystic Fibrosis Transmembrane Conduction Regulator): Senna glycoside A can activate CFTR channels in intestinal epithelial cells, promote chloride ion secretion, bring water into the intestinal lumen, and increase intestinal fluid secretion.

• SLC9A3 (Sodium Hydrogen Exchanger Type 3): Regulates sodium ion absorption, affects the water-salt balance in the intestinal lumen, and promotes water excretion.

• AQP3, AQP4, AQP8 (aquaporins): Senna glycoside A regulates the expression and function of these aquaporins, improves intestinal water transport efficiency, and softens stool.

The synergistic effect of these targets enables senna glycoside A to effectively promote the excretion of intestinal contents and relieve constipation.

Anti-HIV-1 mechanism

Senna glycoside A directly inhibits the DNA polymerase activity of HIV-1 reverse transcriptase and RNase H activity, blocking the key step of viral RNA reverse transcription into DNA, thereby suppressing viral replication. The specific mechanisms include:

• Binds to the active site of reverse transcriptase to block the polymerization process of nucleotides.

• Inhibits RNase H activity, prevents degradation of viral RNA templates, and affects viral genome replication.

This dual inhibitory mechanism gives senna glycoside A a unique advantage in the anti-HIV-1 field.

Druggability evaluation and pharmacokinetics

Efficacy evaluation

Senna glycoside A has a relatively large molecular weight (862.7460) and a high TPSA (347.96), indicating strong polarity and good water solubility (0.7073), but may limit its oral bioavailability and membrane permeability. Its LogP value is 0.8253, indicating moderate lipid solubility, which is beneficial for drug distribution.

The low permeability of the blood-brain barrier suggests it is difficult to enter the central nervous system, reducing the risk of central nervous system side effects. hERG channel inhibition was negative and Ames test was zero, indicating low cardiotoxicity and genotoxicity risks and good safety.

Pharmacokinetic characteristics

Currently, there is limited systematic pharmacokinetic research on senna glycoside A. Literature has shown that after oral administration of senna glycoside A, it is hydrolyzed by the gut microbiota into active anthraquinone metabolites, which exert a laxative effect. Its large molecular weight and polarity may lead to limited intestinal absorption, mainly affecting local intestinal areas. Liver metabolism and distribution in the body require further research.

Prospects and outlooks for clinical applications

Senna glycoside A, as the main active ingredient in traditional laxatives, has been widely used clinically for the treatment of constipation, with proven efficacy and good safety. With further in-depth research into its anti-HIV-1 activity, senna glycoside A is expected to be developed as a naturally derived antiviral drug, with potential value especially in the field of reverse transcriptase inhibitors.

Future research should focus on:

• Optimizing the formulation and administration route of senna glycoside A to improve its bioavailability and targetability.

• Systematically evaluate its in vivo efficacy and safety against HIV-1, and conduct preclinical and clinical trials.

• Explore its anti-inflammatory, anti-tumor, and other potential pharmacological activities to expand its range of applications.

• Combining modern drug design technologies, we develop structurally modified derivatives to enhance activity and pharmacokinetic performance.

Conclusion

Senna glycoside A, as a typical natural anthraquinone glycoside compound, demonstrates broad medicinal value due to its remarkable laxative effect and emerging anti-HIV-1 activity. Its excellent safety profile and multi-target mechanism of action provide a solid foundation for its clinical application. In the future, through multidisciplinary research and technological innovation, it is expected to promote the transformation of senna glycoside A from traditional laxatives to antiviral and multifunctional drugs, advancing the development and application of natural product pharmacology.