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Senna (Senna alexandrina Mill.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomic Classification and Nomenclature

Senna alexandrina Mill., commonly known as Alexandrian senna or Indian senna, is a species of flowering plant in the family Fabaceae, subfamily Caesalpinioideae. The most commonly used species are Senna alexandrina (also known as Cassia senna or Cassia angustifolia), widely recognized for its potent laxative properties. These synonyms reflect a long-standing taxonomic reclassification from the genus Cassia to Senna; the older names Cassia acutifolia (Alexandrian or Khartoum senna) and Cassia angustifolia (Indian or Tinnevelly senna) remain in wide pharmacological use. There are nearly 200 different species of senna.

The name "Senna" is believed to originate from the Arabic word "sana," reflecting its prominence in traditional Arab medicine. The plant derives its name from the Arabic "sena" and from the Hebrew word "cassia," which means "peeled back," a reference to its peelable bark.

Native to the subtropical regions from the Sahara and Sahel across North Africa, the Arabian Peninsula, and extending to the Indian subcontinent, it has been introduced to various other areas including parts of the Americas and Southeast Asia for cultivation.

Botanical Morphology

Senna is a 1–2 m high, undershrub legume plant with pale green to light brown erect, smooth stem with long branches. The plant typically features pinnate leaves and vibrant yellow flowers. Its primary application lies in its laxative properties derived from its leaves and pods.

Common Preparations and Dosage Forms

In traditional medicines, senna is used as a tea, an extract, or syrup; modern uses provide the extract in pill form. Ancient artifacts suggest senna was preserved and used as an herbal wine, and taken as powders, decoctions, and syrups. Contemporary commercial forms include standardized tablets (various sennoside concentrations), oral liquids, granules, and herbal teas. Senna is used in many over-the-counter laxatives in combination with other agents under trade names such as Ex-Lax, Fletcher's Castoria, and Senokot.

2. Traditional and Historical Use

Ancient and Medieval World

The earliest recorded use of senna dates back to two Arab physicians during the 9th century. Once in use, senna popularized rapidly; wild collected in southern Egypt and carried by camel caravans to the Nile or to Red Sea ports. The medicinal uses of senna have been documented since around the 9th century AD by Arabian physicians. More recently, its residue has been found in Egyptian pottery jars dating to about 3150 BCE.

By the 1st century CE, the Greek physician Pedanius Dioscorides referenced senna in his seminal work De Materia Medica, describing it as an Egyptian plant effective as a laxative when prepared from its leaves and pods, influencing subsequent Greco-Roman pharmacological traditions. These ancient applications established senna as one of the earliest known herbal laxatives, often administered as infusions for bowel evacuation. The plant's trade evolved significantly from the 9th century AD, when Arabian physicians facilitated its export from Alexandria, Egypt, through Red Sea ports.

Arabian physicians are credited for bringing senna into the European medical system, and since then, many formulas have been made to round out senna's stimulating effects.

Ayurvedic and Unani Medicine

Senna has been used in traditional medicine for centuries, particularly in Ayurvedic, Unani, and Western herbal medicine systems. It is an important medicinal plant that has been widely used in Ayurveda. In Ayurvedic medicine it is known as Sonamukhi or Swarnapatri and is considered to have purgative (virechana) properties. It is native to Saudi Arabia, Egypt, Yemen, and extensively cultivated in Pakistan; it is a medicinal herb used traditionally to cure a number of diseases like liver diseases, constipation, typhoid, and cholera.

Use in Egyptian and Arab Cultures

Egyptians included senna pods and leaves in their pharmacopoeia as early as the 9th century AD. It was commonly used as a purgative and to prepare the body for religious rituals or detoxification. Historical records show that senna was traded along the Nile River, indicating its widespread use.

Traditional Uses Beyond Laxation

In traditional medicine, senna has also been employed as a diuretic, blood cleanser, and treatment for skin conditions; beyond its laxative properties, senna served as a purgative for bilious disorders, an anthelmintic for deworming intestinal parasites, and a remedy for skin conditions such as ringworm, typically applied topically as a leaf poultice. Ethnopharmacological research around the world accepts senna not only as a laxative but also as a treatment for digestive, respiratory, and nervous system problems, skin problems, and weight loss.

Civil War and 19th-Century Western Medicine

When properly prepared, senna was one of the best, most pleasant, mild, and effective laxatives and was frequently used by pregnant women, persons afflicted with chronic constipation, hemorrhoids and other diseases of the rectum, and constipation occurring when recovering from fevers and other acute diseases. The fluid extract was the most concentrated and active of all senna preparations, made by mixing 16 ounces of moderately fine senna powder with 8 ounces of coarse powdered sugar and diluted in a sufficient quantity of alcohol.

3. Key Constituents and Active Compounds

Anthraquinone Glycosides (Sennosides)

Senna's primary active compounds are anthraquinone glycosides, commonly referred to as sennosides. The dried herbal material has a chemical content of not less than 3.4% hydroxyanthracene glycosides, estimated as sennoside B. Sennosides A and B (2.5%), which are rhein-dianthrone di-glycosidic aminoanthraquinones, are the principal active ingredients.

The active principle of senna was first isolated and characterized by Stoll in 1941. The first two glycosides were identified and attributed to the anthraquinone family. These were found to be dimeric products of aloe emodin and/or rhein, which were named sennoside A and sennoside B. They both hydrolyze to give the aglycones sennidin A and B and two molecules of glucose. Later work confirmed these findings and further demonstrated the presence of sennosides C and D. Small quantities of monomeric glycosides and free anthraquinones seem to be present as well.

Sennoside A and B are stereoisomers of each other. They are dimeric glycosides with rhein dianthrone as aglycone. In sennoside B, the aglycone is in meso form, whereas in sennoside A, it is dextro-rotatory. They also differ by the way of linkage of glucose to the aglycone fraction.

Naphthalene Glycosides

Two naphthalene glycosides isolated from senna leaves and pods are 6-hydroxymusizin glucoside and tinnevellin glucoside. Both compounds can be utilized to distinguish between the Alexandrian and Indian (Tinnevelly) varieties.

Additional Phytochemical Constituents

Cassia angustifolia contains anthraquinones (dianthrone glycosides and sennosides), carbohydrates (polysaccharides and mucilage), flavonoids (isorhamnetin and kaempferol), glycosides (6-hydroxymusizin and tinnevellin), and other constituents. Various flavonoids including kaempferol and isorhamnetin have been isolated from both leaves and pods. The active constituents of the pods are similar to those of the leaves but present in larger quantities.

4. Mechanism of Action

Prodrug Activation by Colonic Bacteria

The β-linked sennosides (and also glycosides from rhubarb or frangula) are not absorbed in the upper gut; they are converted by bacteria of the large intestine into the active metabolite (rhein anthrone). Senna is an inactive glycoside which passes unabsorbed and unchanged through the small bowel and is hydrolyzed by bacterial glycosidases in the large bowel to yield active compounds. Thus, senna has no effect on the small bowel but becomes active in the large bowel. Differences in bacterial flora may be partly responsible for differences in individual responses.

Dual Mechanism: Motility and Secretion

Its rhein-anthrone-induced laxative effects occur through two distinct mechanisms: an increase in intestinal fluid transport, which causes accumulation of fluid intraluminally, and an increase in intestinal motility. The mechanisms of action are firstly an influence on the motility of the large intestine (stimulation of peristaltic contractions and inhibition of local contractions) resulting in accelerated colonic transit, thus reducing fluid absorption; secondly, there is an influence on secretion processes (change in absorption and secretion of water; retention of potassium, stimulation of active chlorine secretion) resulting in enhanced fluid secretion.

The main mechanism is that the sennoside A-derived metabolite, rhein anthrone, could activate macrophages in the colon to secrete prostaglandin E2 (PGE2), which in turn acts as a paracrine factor to downregulate the levels of AQP3 (aquaporin-3) in the epithelia of colon mucosa. Aquaporins (AQPs), a family of membrane proteins, can form water channels on the cell membrane and play a key role in regulating water transport within and between cells.

More recent evidence shows that stimulant laxatives alter fluid and electrolyte absorption, producing net intestinal fluid accumulation and laxation. They increase concentrations of cyclic 3′,5′-adenosine monophosphate (cAMP) in colonic mucosal cells and may alter the permeability of these cells and mediate active ion secretion, producing net fluid accumulation and laxative action.

Onset of Action

The gut bacteria convert sennosides into rheinanthrone and rhein, the active metabolites responsible for the laxative effect. Over 90% of sennosides and their metabolites are excreted in the feces. Sennoside derivatives act mainly in the large intestine, directly stimulating the myenteric plexus and increasing water and electrolyte secretion, thus stimulating peristaltic activity. Their action extends over 6–12 hours.

An interaction between rhein anthrone, the active metabolite of the sennosides, and the immune cells of the colon is suggested as a basis for laxative activity.

5. Scientific Evidence by Area of Use

5.1 Constipation (General and Chronic)

Senna is approved by the U.S. Food and Drug Administration as an over-the-counter laxative and is commonly used to relieve constipation and prepare the bowel for medical procedures such as colonoscopy. The clinical evidence for senna in the treatment of constipation is among the most robustly established of any herbal laxative.

More recent studies using stimulant laxatives (bisacodyl, sodium picosulfate, and senna) have yielded improved levels of evidence and grade recommendations. The current systematic review identified level I evidence with a grade A recommendation for senna. Senna is one of only two OTC agents with level I evidence and grade A recommendations (alongside PEG).

In a clinical trial of standardized senna tablets (Senokot) in the immediate postpartum period, successful treatment of constipation was achieved in 93% of one patient group and 96% of another, significantly better than the success rates of 51% and 59% achieved in controls treated with placebo. Minor abdominal cramps occurred in approximately 13% of patients treated with standardized senna, and in 4% of controls given placebo. There is no evidence to suggest that standardized senna has any effect whatsoever on a breast-fed baby if taken by the mother.

Thirty geriatric long-stay patients aged 65–94 years participated in a trial examining bulk laxative plus senna (Agiolax) in the treatment of chronic constipation, using lactulose (Levolac) as reference medicine. Bulk laxative plus senna (daily doses 14.8 g) produced significantly more frequent bowel habits (4.5 vs. 2.2–1.9 per week) than lactulose (daily doses 20.1 g). Both laxatives proved to be safe, and the study indicated bulk laxative plus senna to be more efficient in treating constipation in geriatric long-stay patients.

A systematic review of 7 controlled trials of laxatives in 444 adults with chronic constipation found all agents equally effective and with no serious adverse events, with common side effects being gastrointestinal discomfort, flatulence, and diarrhea.

5.2 Opioid-Induced Constipation

There is very limited evidence (but much clinical consensus) that sennosides are as effective as lactulose in the management of opioid-induced constipation, but lactulose has an unpleasant taste, generates intestinal gas leading to bloating, and sometimes explosive diarrhea. Senna is widely used in palliative care to manage constipation in patients receiving opioid analgesics, though the formal evidence base from high-quality RCTs specifically in this setting is limited. A retrospective cohort study compared patients who received senna to similar patients who received other oral bowel medications, examining the subsequent risk of "problematic constipation" in hospitalized pediatric oncology patients under 21 years of age in 78 children's and adult hospitals between 2006 and 2011 who were started on seven or more consecutive days of opioid therapy.

5.3 Bowel Preparation for Colonoscopy

A systematic review and meta-analysis was conducted to synthesize data on whether using a senna bowel preparation regimen enhances bowel cleanliness. Databases including MEDLINE, PubMed, Embase, Cochrane Library, and Scopus were searched (from inception to August 2021). The primary efficacy outcome was bowel cleanliness and secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria, encompassing 3,343 patients. Overall, the review found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% CI]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (OR 1.66 [1.08, 2.54], p = 0.02) and compliance (OR 3.05 [1.42, 6.55], p = 0.004). The senna regimen yielded a significantly greater proportion of no nausea and less vomiting. Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

One prospective audit found that the addition of senna to the bowel preparation protocol with magnesium citrate significantly improves the cleansing outcome.

For pediatric colonoscopy, a meta-analysis identifying three RCTs (318 patients) found that PEG was a preferred protocol of bowel preparation compared with senna (risk ratio 1.35, 95% CI 1.05–1.74), and was less painful than senna (RR 0.62, 95% CI 0.44–0.87). No serious adverse events were noted. Overall, the certainty of the evidence was low to moderate.

5.4 Irritable Bowel Syndrome (IBS)

One evaluated study could not prove the efficacy of senna leaves in irritable bowel syndrome: the study treatment was a combination product and the differences between the groups concerning the primary efficacy parameter were not statistically significant. Based on the results of this study, it is not possible to recommend the specific indication "irritable bowel syndrome." The EMA's assessment has therefore not endorsed IBS as an approved indication for senna leaf preparations. People also use senna for irritable bowel syndrome (IBS), hemorrhoids, weight loss, and many other conditions, but there is no good scientific evidence to support these uses.

5.5 Other Investigated Areas (Preliminary or Preclinical Evidence Only)

Sennoside A is a natural dianthrone glycoside mainly from medicinal plants of Senna and Rhubarb. Accumulating evidence suggests that sennoside A possesses numerous pharmacological properties, such as laxative, anti-obesity, hypoglycemic, hepatoprotective, anti-fibrotic, anti-inflammatory, anti-tumor, anti-bacterial, anti-fungal, anti-viral, and anti-neurodegenerative activities. It must be emphasized that these activities are largely based on preclinical (in vitro or animal) studies, and robust human clinical evidence for these expanded indications is lacking.

In Brazilian culture, the senna genus has been used as folk medicine because of its antitumor, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant activities. These ethnopharmacological associations have generated in vitro and animal-model investigations; however, they have not been validated in controlled human clinical trials to a degree that would support therapeutic claims.

6. Body Systems and Health Areas Associated with Senna

Gastrointestinal System

The gastrointestinal system is the primary domain of senna's established pharmacological activity. Senna mainly promotes evacuation of the colon. Its use spans the management of acute and chronic constipation, bowel preparation prior to diagnostic or surgical procedures, constipation in the postpartum period, constipation in geriatric populations, and constipation associated with opioid analgesia in palliative care settings.

Hepatic System

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. The liver injury due to senna has been attributed to the anthraquinone derivatives present in the herbal extract, and most cases have been associated with taking excessive doses, suggesting a direct hepatotoxic rather than idiosyncratic etiology. Liver injury from long-term senna use is rare, and most cases have been self-limited and rapidly reversible upon stopping the laxative. However, cases with a severe course with signs of acute liver failure have been described.

Renal and Electrolyte Systems

Prolonged use and overdose can result in diarrhea, extreme loss of electrolytes, especially potassium, damage to the surface epithelium, and impairment of bowel function by damage to autonomic nerves. Prolonged use or overdose may result in electrolyte and metabolic disturbances (such as hypokalemia, hypocalcemia, and metabolic acidosis or alkalosis), vomiting, muscle weakness, persistent diarrhea, malabsorption, and weight loss.

Colonic Mucosa

Abuse of senna has been associated with melanosis coli, but resolution occurs 8–11 months after withdrawal. Chronic use may cause pathologic changes including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae. "Cathartic colon" with atony and dilation of the colon, especially of the right side, has occurred with habitual use (often for several years) and often resembles ulcerative colitis.

7. Dosage Forms and Dosages Reported in Studies

Standardized Sennoside Content

In the USA, the standard senna tablet contains 8.6 mg of sennosides and the syrup contains 8.8 mg/5 mL; in the UK, the tablet contains 7.5 mg and the syrup 7.5 mg/5 mL.

Adult OTC Dosing as Reported

For the relief of occasional constipation in adults: oral liquid (8.8 mg/5 mL): 10 to 15 mL orally once a day (maximum 30 mL/day); tablets with sennosides 8.6 mg: 2 tablets orally once a day at bedtime (maximum 8 tablets/day); tablets with sennosides 15 mg: 2 tablets orally once a day to 2 times a day. For 20 mg sennoside tablets, 1 tablet orally once a day; for 25 mg sennoside tablets, 2 tablets once a day to twice a day. This drug usually produces effects within 6 to 12 hours.

The typical dose is 15 to 30 mg of sennosides twice a day, and it is recommended for short-term use only (less than one week).

Senna is most often used by adults in doses of 17.2 mg sennosides by mouth, once or twice daily.

Pediatric Dosing

Children ages 2–5 should not take more than 8.6 mg sennosides twice daily. Senna is an FDA-approved nonprescription (OTC) drug for adults and children ages 2 years and older.

Bowel Preparation for Colonoscopy

One study used X-Prep®, a senna fruit dry extract preparation corresponding to 150 mg hydroxyanthracene glycosides, calculated as sennoside B, per single dose, for colon cleansing.

Breastfeeding Data

Twenty-five nursing mothers averaging 4.7 months postpartum were given a single 100 mg senna tablet containing 8.6 mg of sennosides A and B (Senokot). Milk was expressed every 30 minutes for 6 hours. Sennosides A and B were undetectable (<0.34 mg/L) in all samples of breast milk. Three mothers whose infants reportedly had loose stools were subsequently given a double dose of the tablets, but sennosides A and B remained undetectable.

Palliative Care

In clinical trials, 83% of participants reduced their dose from the studied 1 g daily due to side effects, indicating that lower doses are typically better tolerated.

Duration of Therapy

Senna is possibly unsafe when used for longer than 1 week or in doses above 34.4 mg sennosides twice daily. Long-term use can cause the bowels to stop functioning normally and might cause dependence on laxatives.

8. Safety Considerations and Drug Interactions

General Safety Profile

The safety and efficacy of senna have been reviewed. Tolerance and genotoxicity do not seem to be problems associated with senna, especially when used periodically in therapeutic doses. A well-defined purified senna extract was not carcinogenic when administered orally to rats in daily doses up to 25 mg/kg for 2 years.

Common Adverse Effects

Senna can cause mild abdominal complaints, such as cramps or pain. Other adverse effects are discoloration of the urine and hemorrhoidal congestion. Common side effects of senna include nausea, vomiting, abdominal cramps or pain, gas (flatulence), urgent and frequent bowel movements, diarrhea, urine discoloration, kidney inflammation (nephritis), rash, low potassium level (hypokalemia), melanosis coli, finger clubbing (with chronic use), wheezing, and severe allergic (anaphylactoid) reaction.

Melanosis Coli

Chronic use may result in intestinal mucosa pigmentation/pseudomelanosis coli, which usually recedes with treatment discontinuation. Although still uncertain, sennoside A may cause melanosis coli and subsequent colon cancer. The potential toxic mechanisms involve the aberrant cell proliferation and apoptosis, as well as inflammatory cell infiltration and aberrant crypt foci. However, abuse of senna has been associated with melanosis coli, but resolution occurs 8–11 months after withdrawal.

Electrolyte Disturbances

Electrolyte disturbances may produce vomiting and muscle weakness; rarely, osteomalacia, secondary aldosteronism, and tetany. Chronic use may cause pathologic changes including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae. Hypokalemia, which occurs as the effect of long-term use of laxative drugs, strengthens the effect of cardiac glycosides and interacts with antiarrhythmic drugs.

Hepatotoxicity

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. The liver injury due to senna has been attributed to the anthraquinone derivatives present in the herbal extract, and most cases have been associated with taking excessive doses, suggesting a direct hepatotoxic rather than idiosyncratic etiology.

Drug Interactions

Digoxin: Senna can lower potassium levels, increasing the risk of side effects from digoxin, a medication used to treat heart conditions.

Warfarin: Diarrhea can increase the effects of warfarin and increase the risk of bleeding. If taking warfarin, excessive amounts of senna should not be taken.

Diuretics: Taking senna along with "water pills" might decrease potassium in the body too much. Some "water pills" that can decrease potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), and hydrochlorothiazide (HCTZ).

Estrogens: Some pills used for hormone replacement therapy contain estrone, and senna can reduce the amount of estrone in the body. Other pills contain ethinyl estradiol, and senna can decrease how much estradiol the body absorbs. Taking senna might decrease the effects of hormone replacement therapy.

Antibiotics: Because senna requires bacterial metabolism for activation, concurrent antibiotic use can potentially decrease efficacy by reducing the colonic bacteria that produce the active metabolites.

Herbal combinations: There is concern that senna should not be combined with horsetail or licorice, since this may increase the chance that potassium levels in the body go too low.

Contraindications

Contraindications established in regulatory and clinical literature include patients experiencing a sudden change in bowel movements lasting more than 2 weeks, stomach pain, or nausea or vomiting. Additional contraindications include ileus, bowel obstruction, and known hypersensitivity to anthraquinone compounds.

Pregnancy and Lactation

For treatment of constipation, a dose of 10 to 60 mg at bedtime for a maximum of 10 days has been cited in the second and third trimester. Regarding 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.

Pediatric Safety

A 15 mg/kg dose is potentially toxic in children under 6 years. Over-the-counter use is not recommended in children under 2 years.

References

• NIH LiverTox: Senna — National Institute of Diabetes and Digestive and Kidney Diseases
• NIH LactMed: Senna — Drugs and Lactation Database, National Institute of Child Health and Human Development (Updated November 2024)
• Pharmacology, Toxicology, and Metabolism of Sennoside A, A Medicinal Plant-Derived Natural Compound — PMC / Frontiers in Pharmacology (2021)
• The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis — Gastroenterology Nursing (2022)
• Efficacy and Safety of Over-the-Counter Therapies for Chronic Constipation: An Updated Systematic Review — PMC (2021)
• Polyethylene Glycol Versus Senna for Bowel Preparation for Colonoscopy in Children: Updated Evidence by a Systematic Review and Meta-Analysis — PMC / Cureus (2021)
• Addition of Senna Improves Quality of Colonoscopy Preparation with Magnesium Citrate — PMC (2009)
• Sennoside — ScienceDirect Topics Overview
• Senna alexandrina — ScienceDirect Topics Overview
• Stimulant Laxatives and Opioid-Induced Constipation — Journal of Pain and Symptom Management / ScienceDirect (2012)
• The Genus Senna (Fabaceae): A Review on Its Traditional Uses, Botany, Phytochemistry, Pharmacology and Toxicology — South African Journal of Botany / ScienceDirect (2020)
• Senna (Cassia angustifolia Vahl.): A Comprehensive Review of Ethnopharmacology and Phytochemistry — ScienceDirect (2023)
• Safety and Efficacy of a Bulk Laxative Containing Senna Versus Lactulose in the Treatment of Chronic Constipation in Geriatric Patients — PubMed (1993)
• Standardized Senna in the Management of Constipation in the Puerperium: A Clinical Trial — PubMed (1980)
• The Action of Sennosides and Related Compounds on Human Colon and Rectum — PubMed
• Comparative Effectiveness of Senna to Prevent Problematic Constipation in Pediatric Oncology Patients Receiving Opioids — PubMed (2014)
• Cytotoxicity of Rhein, the Active Metabolite of Sennoside Laxatives, Is Reduced by Multidrug Resistance-Associated Protein 1 — PMC / British Journal of Cancer (2002)
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• Ethnobotanical Description and Biological Activities of Senna alata — PMC (2020)
• Randomized Clinical Trial of a Phytotherapic Compound Containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia for Chronic Constipation — PMC (2010)
• Senna: As Immunity Boosting Herb Against Covid-19 and Several Other Diseases — PMC (2023)
• Senna Dosage Guide — Drugs.com
• Senna Monograph for Professionals — Drugs.com
• Pharmacologically Active Flavonoids from the Anticancer, Antioxidant and Antimicrobial Extracts of Cassia angustifolia Vahl — PMC (2016)