Sennoside A has the ability to inhibit several versions of RDDP and RNase H. It has been observed that IC50s of 78 μM (K103N RT), 21.3 μM (Y181C RT), and 64 μM (Y188L RT) for various variants of RDDP are inhibited. 18.4 μM for N474A RT and 17.7 μM for Q475A RT, respectively, were the IC50s[3]. HIV-1 recombinant CAT virus, pseudotyped with the envelope glycoprotein of the laboratory-adapted T-tropic virus HXBc2, infects Jurka cells. Infected cells' CAT activity is greatly inhibited by sensnoside A (5–20 μM; 72 h)[3].

Type 2 diabetes (T2D) mice's gut microbiome composition is changed by sensnoside A (25 mg/kg, 50 mg/kg; intragastric gavage for 12 weeks), which also has anti-obesity effects[3]. In the ileum of genetically faulty animals, sensnoside A also raises tight junction proteins and decreases inflammation[3].

Hepatotoxicity
Use of senna in the recommended doses for a limited period of time has been associated with few side effects, most of which are mild and transient and related to its laxative action. With longer term and higher dose use of senna, however, adverse events have been described including several cases of clinically apparent liver injury. The time to onset of liver injury was usually after 3 to 5 months of use, and the pattern of serum enzyme elevations was hepatocellular. The liver injury was usually mild-to-moderate in severity and resolved rapidly with discontinuation. In at least one instance, reexposure led to rapid recurrence of liver injury. Immunoallergic features and autoimmune markers were not present in the published cases.
In addition, a related plant commonly known as coffee senna or Cassia orientalis has been linked to many instances of acute, severe toxicity with encephalopathy, myopathy and hepatic dysfunction. Outbreaks of “hepato-myo-encephopathy” of unknown cause among children occurred yearly in Uttar Pradesh, India typically between September and November. Investigation eventually identified Cassia occidentalis ingestion as the probable cause, typically occurring in children who eat the leaves or pods of the common flowering weed. While Cassia occidentalis has also been used to prepare tea, the amount ingested was minimal. In children, and rarely in adults, the presentation was precipitous with nausea, vomiting, tremor, abnormal and violent behavior, grimacing and self-mutilation followed by stupor and coma at which time serum aminotransferase and bilirubin levels were typically elevated. In severe instances, the liver injury was progressive, serum ammonia and INR levels rose and patients developed coma, convulsions and status epilepticus that was unresponsive to therapy. Autopsies revealed hepatic necrosis and cholestasis. A similar pattern of symptoms and injury occurs in animals that consume Cassia occidentalis. Whether this syndrome has a similar pathogenesis to the rare instance of hepatic injury attributed to typical senna (Cassia acutifolia or angustifolio) that is used as a laxative is unknown.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although an early uncontrolled report using an old senna product found increased frequency of diarrhea in breastfed infants, several controlled studies using modern senna products found no effect on the infant. Usual doses of senna are acceptable to use during breastfeeding.
◉ Effects in Breastfed Infants
After administration of 3.6 mL of senna fluidextract on day 5 postpartum, a laxative effect on the bowels was observed in 6 of 10 infants.
In another observational study, no cases of diarrhea were observed among the breastfed infants of 148 mothers who received 2 teaspoonfuls of Senokot (equivalent to 700 mg of senna pod) on day 3 postpartum.
Fifty mothers who were in the first day postpartum received senna equal to 450 mg of senna pod. Additional doses were given on subsequent days if needed. None of their breastfed infants were noted to have any markedly abnormal stools, although all of the infants also received supplemental feedings.
In a randomized, nonblinded study, 35 mothers were given tablets containing a total of 14 mg of standardized senna extract once daily for 2 weeks starting in the immediate postpartum period. Six of the 37 breastfed infants were reported to have diarrhea which was a higher percentage than with other nonabsorbable laxatives in the study.
Sixteen women were given 800 mg of powdered senna containing 24 mg of sennosides. None of their breastfed infants had any abnormal stools.
A randomized, double-blind trial compared commercial senna tablets (Senokot) in a dose of 2 tablets (14 mg sennosides a and b) twice daily for 8 doses started on the first day postpartum to placebo. Of the women in the study, 126 breastfed their infants and took senna while 155 control mothers breastfed their infants. There was no difference in the percentages of infants in the active and control groups with loose stools or diarrhea.
Twenty postpartum mothers were given a laxative containing plantango seeds (psyllium) and senna equivalent to 15 mg of sennosides a and b daily on days 2 to 4 postpartum. Of the 11 infants who were breastfed, none had any loose stools.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Next Generation Sequencing and Transcriptome Analysis Predicts Biosynthetic Pathway of Sennosides from Senna (Cassia angustifolia Vahl.), a Non-Model Plant with Potent Laxative Properties. PLoS One. 2015 Jun 22;10(6):e0129422.

[2]. Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391.

[3]. Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391.

[4]. Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits. Oxid Med Cell Longev. 2020 Jun 25;2020:2375676.

Senna (powdered) is a yellow-brown powder with a slight odor and taste. (NTP, 1992)
Sennoside A is a member of the class of sennosides that is rel-(9R,9'R)-9,9',10,10'-tetrahydro-9,9'-bianthracene-2,2'-dicarboxylic acid which is substituted by hydroxy groups at positions 4 and 4', by beta-D-glucopyranosyloxy groups at positions 5 and 5', and by oxo groups at positions 10 and 10'. The exact stereochemisty at positions 9 and 9' is not known - it may be R,R (as shown) or S,S. It is a member of sennosides and an oxo dicarboxylic acid.
Senna (Cassia species) is a popular herbal laxative that is available without prescription. Senna is generally safe and well tolerated, but can cause adverse events including clinically apparent liver injury when used in high doses for longer than recommended periods.
Sennoside A has been reported in Rheum palmatum, Rheum tanguticum, and other organisms with data available.
Senokot is a standardized, concentrated preparation, by Purdue, containing the anthraquinone glycosides sennosides extracted from senna leaves with laxative activity. Sennosides act on and irritate the lining of the intestine wall, thereby causing increased intestinal muscle contractions leading to vigorous bowel movement.
Preparations of SENNA PLANT. They contain sennosides, which are anthraquinone type CATHARTICS and are used in many different preparations as laxatives.

C42H38O20

862.74

862.195

81-27-6

73111

Light yellow to yellow solid powder

1.7±0.1 g/cm3

1144.8±65.0 °C at 760 mmHg

200-240ºC

348.6±27.8 °C

0.0±0.3 mmHg at 25°C

1.763

1.88

12

20

9

62

1550

12

C1=CC2=C(C(=C1)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)C(=O)C4=C([C@@H]2[C@@H]5C6=C(C(=CC=C6)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O)O)O)C(=O)C8=C5C=C(C=C8O)C(=O)O)C=C(C=C4O)C(=O)O

IPQVTOJGNYVQEO-KGFNBKMBSA-N

InChI=1S/C42H38O20/c43-11-23-31(47)35(51)37(53)41(61-23)59-21-5-1-3-15-25(17-7-13(39(55)56)9-19(45)27(17)33(49)29(15)21)26-16-4-2-6-22(60-42-38(54)36(52)32(48)24(12-44)62-42)30(16)34(50)28-18(26)8-14(40(57)58)10-20(28)46/h1-10,23-26,31-32,35-38,41-48,51-54H,11-12H2,(H,55,56)(H,57,58)/t23-,24-,25-,26-,31-,32-,35+,36+,37-,38-,41-,42-/m1/s1

(9R)-9-[(9R)-2-carboxy-4-hydroxy-10-oxo-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9H-anthracen-9-yl]-4-hydroxy-10-oxo-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9H-anthracene-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 6.25 mg/mL (7.24 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)