Simaruba

Other Names

Acajou blancAccitunoAceitilloAceitunaAceitunoAceituno negritoAdonichiAdoonsideroAkuAlmácigoAlmacigo blancoAlmacigo coloradoAmerican elemiArubaAssoumaripaBalsamoBitter ashBitter damsonBitter woodBitterescheBitterwoodBitterwood treeBois amerBois blancBois d'encensBois freneBois negresseBrazilian elemiBrazilian white pineBursera arboreaBursera bonairensisBursera gummiferaBursera gummifera var. glabrataBursera gummifera var. polyphyllaBursera gummifera var. pubescensBursera integerrimaBursera ovalifoliaBursera simarubaBursera simaruba var. yucatanensisBursera subpubescensBurseria gummiferaCachibouCaixetaCajú-ranaCaranaCarateCedro amargoCedro blancoChacaChibouChiriuanaCopperwoodCortex simarubaCunaCupania glabrataDaguillaDaguilloDamsonDysentery barkElaphrium arboreumElaphrium integerrimumElaphrium ovalifoliumElaphrium simarubaElaphrium subpubescensFlambeauFragon caranneGavilanGomartGommierGommier blancGommier rougeGuitarroGumbo limboHualajaIcicariba simarubaIndio desnudoJamaica barkJoboJocoteJocote de micoJuan primeroJucumicoLarge gommier treeLowland gommierMalacachetaMaroubaMarubaMarupaMarupáMarupuabaMegritoMountain damsonNaked IndianNegritoOlivoOlivo amargoOrinoco simaroubaPa'asaak'ilPaljul'tePalo amargoPalo blancoPalo chinoPalo jiotePalo mulatoPao pombaParadise treeParahybaParaibaPasa-akPasacPasaquePau parahybaPazaquePicraena officinalisPistacia americanaPistacia simarubaPitombaQuassia alatifoliaQuassia dioicaQuassia glaucaQuassia simaroubaQuassia simarubaRabo de lagarto blancoRed birchRobaRoblecilloShirimaSimabaSimaroubaSimarouba amaraSimarouba amara var. opacaSimarouba amara var. puberulaSimarouba amara var. typicaSimarouba amerSimarouba glaucaSimarouba médicinalSimarouba medicinalisSimarouba officinalisSimarouba opacaSimarrubaSimaruba amaraSimarupaSimereSlave woodSoemaroebaSoemaroepaStave woodStavewoodSumaruppaTalchocoteTamanqueiraTapirira macrophyllaTerebinthus arboreaTerebinthus simarubaTourist treeTurpentine treeWalkaraWest Indian birchWing-leaved quassiaWinged-leaved quassiaXpa'saak'XpasakYakuZapateroZwingera amara

Synopsis

Simarouba (Simarouba glauca DC.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomic Classification and Nomenclature

Simarouba glauca DC. belongs to the family Simaroubaceae and is generally known as the paradise tree. The abbreviation "DC" in the accepted binomial refers to Augustin Pyramus De Candolle, a Swiss botanist who made significant contributions in describing and classifying the plant. The Simaroubaceae family includes 32 genera and further 170 species of trees. The genus name Simarouba encompasses several medicinally relevant species; among the simarouba plants, there may be mentioned Simarouba amara Aubl., Simarouba glauca, Simarouba versicolor, and Simarouba excelsa.

Common Names

Common names include paradise-tree, dysentery-bark, and bitterwood. In India, it is referred to as Lakshmi taru, symbolizing prosperity and medicinal value in local traditions. In Spanish-speaking areas of Central and South America, the name aceituno is prevalent, derived from the fruit's resemblance to olives. Additional vernacular names include "Laxmitaru," "bitter ash," "bitter damson," and "princess tree."

Botanical Description and Habitat

Simarouba glauca is a flowering tree that is native to Florida, South America, and the Caribbean. Simarouba glauca is an evergreen tree in the family Simaroubaceae, typically growing to 15 meters tall with a narrow crown and straight bole, native to the understory of moist or dry tropical forests from Mexico through Central America to Panama and in the Caribbean from Cuba to southern Florida. This species thrives in a variety of habitats, including thickets, rocky hillsides, and stream beds at elevations up to 900 meters, preferring well-drained sandy or calcareous soils with a pH range of 5.5 to 8.5, and it is notably shade-tolerant and fast-growing.

It is suited for a temperature range of 10 to 40 °C (50 to 104 °F), and can grow at elevations from sea level to 1,000 m (3,300 ft). It bears yellow flowers and purple elongated oval fleshy fruits. The specific name glauca means "covered with bloom," which refers to the bluish-green foliage.

Geographic Spread and Cultivation

Simarouba forms an important source of edible oil for various South and Central American countries and is widely grown in countries like Costa Rica, El Salvador, Honduras, Cuba, Nicaragua, Mexico, Haiti, and Jamaica. Cultivation of simarouba was introduced in India by the National Bureau of Plant Genetic Resources as a potential source of vegetable oil during the late sixties in the sub-humid climate of Orissa. Later in the seventies, the cultivation of simarouba spread to semi-arid, dry, and saline land areas of other Indian states like Gujarat, Maharashtra, Tamil Nadu, Karnataka, and Andhra Pradesh.

Plant Parts Used and Common Preparations

The main therapeutic constituents have been identified in simarouba's bark, leaves, roots, and fruit seeds. Its leaves are alternate and pinnate, flowers are small and yellowish in panicles, and the fruit is a drupe containing an edible but inferior nut that yields 60–75% oil suitable for culinary and industrial uses. Common preparations documented in traditional and research contexts include aqueous decoctions and infusions of the bark and leaves, solvent extracts (methanol, ethanol, ethyl acetate, chloroform, petroleum ether, and hexane), seed oil obtained by mechanical expelling or solvent extraction, and dried leaf or bark powder.

2. Traditional and Historical Use

Indigenous and Pre-Colonial Americas

The leaves and bark of simarouba have long been used as a natural medicine in the tropics. Simarouba was first imported into France from Guyana in 1713 as a remedy for dysentery. When France suffered a dysentery epidemic from 1718 to 1725, simarouba bark was one of the few effective treatments. French explorers "discovered" this effective remedy when they found that the indigenous Indian tribes in the Guyana rainforest used simarouba bark as an effective treatment for malaria and dysentery.

Other indigenous tribes throughout the South American rainforest use simarouba bark for fevers, malaria, and dysentery, as a hemostatic agent to stop bleeding, and as a tonic. Indigenous Amerindian tribes of the rainforest used it as a hemostat to stop bleeding, for fevers, and against dysentery.

Cuba and the Caribbean

In Cuba, where it is called gavilan, an infusion of the leaves or bark is considered to be astringent, a digestion and menstrual stimulant, and an antiparasitic remedy. It is taken internally for diarrhea, dysentery, malaria, and colitis; it is used externally for wounds and sores.

Belize

In Belize the tree is called "negrito" or "dysentery bark." There, the bark (and occasionally the root) is boiled in water to yield a powerful astringent and tonic used to wash skin sores and to treat dysentery, diarrhea, stomach and bowel disorders, hemorrhages, and internal bleeding.

Brazil

In Brazil it is employed against fever, malaria, diarrhea, dysentery, intestinal parasites, indigestion, and anemia. In Brazilian herbal medicine, simarouba bark tea has long been the most highly recommended natural remedy against chronic and acute dysentery.

Suriname

In Suriname's traditional medicine, the crushed seeds drawn in alcohol are used against snakebites. An infusion (herbal tea) of the bark is used against malaria, rheumatism, shingles, and fever.

Traditional Preparation Methods

A decoction is taken internally in the treatment of diarrhea, dysentery, malaria, fevers, hemorrhages, intestinal parasites, and colitis. The bark (and sometimes the root) is boiled in water to yield an important tonic used to wash skin blisters and to treat dysentery, diarrhea, stomach and bowel diseases, hemorrhages, and internal bleeding.

India and Ayurvedic Context

Since ancient times, S. glauca has been well known for its traditional use in treating cancer, malaria, dysentery, blood and gastric disorders, and infectious diseases, especially in Southern Florida, West Indies, and Brazil. Following its introduction to India in the 1960s, the plant was incorporated into Indian traditional and herbal practice; in Hinduism, Simarouba glauca, or Paradise tree/Lakshmi Taru, symbolizes healing and prosperity, valued for its cancer prevention and treatment properties.

3. Key Constituents and Active Compounds

Quassinoids: The Primary Bioactive Class

The main active group of chemicals in simarouba are called quassinoids, which belong to the triterpene chemical family. Quassinoids are found in many plants and are well known to scientists. The antiprotozoal and antimalarial properties of these chemicals have been documented for many years.

Quassinoids are one of the major active phytochemical constituents that belong to the triterpene family, exhibiting significant pharmacological properties such as antimicrobial, anticancer, antipyretic, and haemostatic activity. These compounds inhibit nucleic acid and protein synthesis.

The tree is a rich source of quassinoids which include ailanthinone, canthin, dehydroglaucarubinone, glaucarubine, glaucarubolone, glaucarubinone, holacanthone, melianone, simaroubidin, simarolide, simarubin, and simarubolide. Quassinoids are a diverse class of highly oxygenated secondary metabolites, identified from natural plant materials mostly in the Simaroubaceae family, which are believed to be biosynthesized through the triterpenoid biogenetic pathway and originating from the oxidative degradation of tetracyclic tirucallane triterpene.

Glaucarubinone

Glaucarubinone is a quassinoid present in the family Simaroubaceae. Simarouba glauca, also known as Laxmitaru or paradise tree, contains glaucarubinone that is known for its medicinal property. Glaucarubinone's main actions are as an anti-cancer agent that inhibits cancer cell proliferation, migration, and invasion by targeting signaling pathways like PAK1 and PAK4.

Additional Quassinoids and Other Alkaloids

The major phyto-constituent of S. glauca was reported to be quassinoids, which is a group of triterpene lactones, including glaucarubin, glaucarubolone, and glaucarubinone. Scopoletin and canthin-6-one and its dimethoxy derivative have been isolated from the wood extract of S. glauca. In addition to quassinoids, β-carboline alkaloids, canthin alkaloids, triglycerides, coumarins, squalene-type triterpenoids, and fatty acids are purified from Simaroubaceae.

Broad Phytochemical Profile

Results of phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, steroids, terpenoids, tannins, glycosides, saponins, carbohydrates, and fixed oils. GC-MS analysis of methanol and chloroform extracts revealed the presence of key constituents such as flavonoids, alkaloids, glycosides, and quinic acid.

Seed Oil Composition

The fatty acid composition and iodine value of the oil indicate that it possesses saturated (40.8–42.6%), monounsaturated (52.9–55.0%), and polyunsaturated (2.5–3.4%) fatty acid in ratios close to that of palm oil. Simarouba glauca seed oil is one of the high-content seed oils having oleic acid as a rich source of fatty acid, with palmitic and stearic acid also present in the triglyceride molecule. Although the seeds contain quassinoids — a toxic compound of the triterpene family — the oil is reported to be free of toxic compounds and is edible.

Mechanisms of Action of Key Compounds

Quassinoids, one of the major active phytochemical constituents, exhibit significant pharmacological properties such as antimicrobial, anticancer, antipyretic, and haemostatic activity. These compounds inhibit nucleic acid and protein synthesis via interference at the peptidyl transferase site or through the downregulation of phosphoribosyl pyrophosphate aminotransferase, which confers anticancer activity.

The mechanism of cell death induction by quassinoids is mediated by: (a) down-regulation of proliferation-inducing proteins, cyclinD1, followed by arresting the cells in G0/G1 or G2/M phase; (b) induction of apoptosis proteins including p53 and caspase-3; (c) halting angiogenesis through VEGF, MIC-1, and IL-8; (d) promoting cellular differentiation; and (e) inhibiting the master regulator of oxidative stress Nrf2. Modulation of these processes leads to the inhibition of tumor cell growth and metastatic spread.

Survival of cancer cells is regulated by the PI3K-Akt pathway. Canthin-6-one inhibits the phosphorylation of AKT, leading to an antiproliferative effect. Tricaproin has been purified and characterized from the chloroform extract of S. glauca. Tricaproin inhibited colorectal cancer cell growth by promoting apoptosis through HDAC inhibition.

4. Scientific Evidence by Area of Use

4.1 Anticancer and Anti-Leukemic Activity

Overview and Early Screening

Early cancer screening performed by the National Cancer Institute in 1976 indicated that an alcohol extract of simarouba root (and a water extract of its seeds) had toxic actions against cancer cells at very low dosages (less than 20 micrograms/milligrams). Following up on that initial screening, scientists discovered that several of the quassinoids in simarouba — glaucarubinone, ailanthinone, and dehydroglaucarubinone — had anti-leukemic actions against lymphocytic leukemia in test tubes and published several studies in 1977 and 1978.

Colorectal Cancer (In Vitro)

All fractions were individually examined for anti-cancer property in cancer cells representing lungs, cervix, breast, colon, and rectum in vitro. Among all fractions tested, the chloroform (SGC) and ethyl acetate (SGEA) extracts showed potent anti-proliferative effects by triggering apoptosis. These findings demonstrate that the extracts SGC and SGEA have potent anti-cancer activities compared to other fractions of S. glauca leaf and thus warrant further pre-clinical studies.

Tricaproin isolated from Simarouba glauca inhibited the growth of human colorectal carcinoma cell lines by targeting class-1 histone deacetylases. This study was published in Frontiers in Pharmacology (2018).

Leukemia (In Vitro)

A study evaluated the apoptotic properties of leaf extracts of Simarouba glauca against human leukemic cancer cells. Cytotoxicity of S. glauca was assessed in the leaf extract of petroleum ether against leukemic cells by MTT assay. Among the four extracts tested, petroleum ether extract showed a higher order of in vitro anticancer activity. The petroleum ether extract strongly inhibited the proliferation of K562 cell lines with IC50 values of 186 µg/mL. Caspase-3 analysis revealed that cell death was due to mitochondrial or death receptor activation. These findings suggested that Simarouba glauca leaf extracts inhibited leukemic cells in a time- and dose-dependent manner either through mitochondrial or death receptor activation.

Lung Cancer (In Vitro)

A study demonstrated the anticancer and apoptotic effect of the leaf extract of petroleum ether (LPE) on human non-small-cell lung cancer A549 cells. MTT assay was used to investigate the effect of LPE on the viability of A-549 cells. The apoptotic effect was evaluated using fluorescence staining, acridine orange/ethidium bromide staining, Hoechst staining, flow cytometry analysis, annexin V staining, and caspase assay. The results showed a direct correlation between dose and the rate of cytotoxicity. Fluorescence staining revealed apoptotic features such as blebbing and chromatin condensation. Caspase 3 expressions indicated that cell death occurred either through the mitochondrial pathway or the death receptor. The study revealed that the LPE induced apoptosis of human non-small-cell lung cancer A549 cells, either through mitochondrial or death receptor pathway.

Breast Cancer (In Vitro)

The methanol extract of S. glauca showed significant cytotoxicity against the MCF-7 breast cancer cell line with an IC50 value of 16.12 µg/mL. A separate study (published in Asian Pacific Journal of Cancer Prevention, 2024) evaluated the effects of bark extract against triple negative breast cancer (MDA-MB-231) cells: the study focused on the evaluation of anticancer effects of S. glauca bark UAE-EA fraction against MDA-MB-231 triple negative breast cancer cell lines. MTT assay was applied to analyse cell viability, and MMP assay confirmed initiation of drug-induced apoptosis. Apoptotic morphology and quantification were assessed by DAPI and Annexin V/propidium iodide (PI) staining.

Oral and Cervical Cancer (In Vitro)

Among all extracts tested, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing oral squamous cell carcinoma (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity.

Evidence Strength — Anticancer: All existing anticancer evidence is preclinical, derived entirely from in vitro cell-line studies and a small number of animal screens. Although the pharmacological potential of Simarouba glauca is well documented, not much is known about the mechanism(s) of action of the isolated phyto-constituents. In addition, many gaps pertaining to the efficacy of pharmacological agents for inhibiting cancers do exist. No human clinical trials on anticancer activity have been identified in the published literature.

4.2 Antimalarial Activity

Extracts prepared from Simarouba amara fruits collected in Panama have been found to be active against Plasmodium falciparum in vitro and against Plasmodium berghei in mice. Four active quassinoids have been identified as ailanthinone, 2'-acetylglaucarubinone, glaucarubinone, and holacanthone.

Dichloromethane fractions were screened for their cytotoxicities on Artemia salina larvae, and 50% inhibitory concentrations were determined for Plasmodium falciparum in in vitro studies. Both chloroquine-susceptible and resistant strains of P. falciparum were significantly inhibited by these excerpts.

Evidence Strength — Antimalarial: Evidence is derived from in vitro and animal (rodent malaria model) studies. The activity against both chloroquine-susceptible and resistant strains is noteworthy, but no controlled human clinical trials have been published for Simarouba glauca extract as an antimalarial agent specifically. The broader traditional use record, together with in vitro and animal data, places this as a promising but unvalidated clinical candidate.

4.3 Anti-Amoebic Activity

Tests were done to detect the antiamoebic action of plant extracts prepared from the traditional Simarouba glauca stems. A landmark in vitro study using microdilution methodology assessed the anti-amoebic activities of Simarouba amara stem extracts and isolated quassinoids against Entamoeba histolytica, establishing minimum inhibitory concentrations for the active fractions (Wright CW et al., Antimicrobial Agents and Chemotherapy, 1988). Simarouba amara Aubl., in particular, is a widespread tree in Guiana whose bark is used by the natives as a remedy for treating dysentery. Chemical Abstracts describes the use of Simarouba amara stalk extract demonstrating antiamoebic activity in vitro.

Evidence Strength — Anti-Amoebic: Evidence is in vitro and preclinical. Traditional use as a dysentery remedy is long-established across multiple cultures, lending ethnopharmacological plausibility. No randomized human trials have been identified.

4.4 Antimicrobial and Antifungal Activity

Antimicrobial activity and Minimum Inhibitory Concentration (MIC) were determined against 14 bacterial and 6 fungal strains. The ethanolic and methanolic extracts showed exclusive activity against S. aureus and profound activity against E. coli and S. marcescens. Methanolic extract demonstrated higher antimicrobial activity with a MIC value of 3.2 mg/mL against the test pathogens.

The extracts demonstrated potential antioxidant activity; methanol extract had higher antioxidant potential compared to the ethanol extract. The major proactive bioactive compound with maximum antioxidant capacity was observed to be terpenoids.

Evidence Strength — Antimicrobial: Preliminary in vitro data only. No clinical trials in humans have been reported.

4.5 Antioxidant Activity

Phytochemical composition of S. glauca leaf extracts and in vitro anti-inflammatory and antioxidant activities were evaluated using standard bioassays. The anti-inflammatory activity was conducted using protein denaturation assay, heat-induced hemolysis, and lipoxygenase inhibitory assays, which revealed IC50 values of 328 µg/mL, 342.6 µg/mL, and 432.1 µg/mL for the aqueous, ethanol, and ethyl acetate extracts, respectively. For antioxidant activity, the aqueous, ethanol, and ethyl acetate extracts demonstrated scavenging activity against DPPH and ABTS radicals, with IC50 values of 180.7 µg/mL, 209.7 µg/mL, and 678.2 µg/mL for DPPH, and 75.3 µg/mL, 83.9 µg/mL, and 225.8 µg/mL for ABTS, respectively.

Evidence Strength — Antioxidant: In vitro only. These results are standard phytochemical characterization data and do not establish clinical antioxidant benefit.

4.6 Anti-Inflammatory Activity

In vitro anti-inflammatory activity was evaluated using albumin denaturation assay and membrane stabilization method. Results indicate that the various bioactive constituents detected in S. glauca may be responsible for its in vitro antidiabetic and anti-inflammatory effects. The various bioactive constituents detected in S. glauca may be responsible for its in vitro antidiabetic and anti-inflammatory effects.

Evidence Strength — Anti-Inflammatory: Exclusively in vitro. S. glauca may be a potential candidate for the development of future antidiabetic and anti-inflammatory compounds; however, further studies and standardization of the plant research may be required to develop it as medicine.

4.7 Skin and Dermatological Applications

The water extract of Simarouba glauca increased skin keratinocyte isolation, improved skin hydration and moisturization, and reduced patchy discoloration in the skin. A US patent (5,676,948) has been issued for the use of a simarouba extract for reducing patchy skin pigmentation, based on the observed effects on keratinocyte biology and skin hydration.

Evidence Strength — Skin: Limited. The patent and associated data represent a proprietary, commercially motivated investigation. Independent clinical validation has not been published in the peer-reviewed literature.

4.8 Hepatoprotective Activity

The pharmacological activity of S. glauca is attributed to its varied phytochemical make-up, which includes quassinoids, alkaloids, flavonoids, and phenolic compounds, which show a broad spectrum of biological processes including anticancer, antimicrobial, anti-inflammatory, antioxidant, and hepatoprotective action. Preliminary pharmacological screening of S. glauca DC leaf extracts for hepatoprotective activity has been reported (John PP et al., World Journal of Pharmacy and Pharmaceutical Sciences, 2016), and a study on Simarouba amara documented a hepatoprotective effect of the aqueous stem bark extract against carbon tetrachloride (CCl4)-induced hepatic damage in rats (Maranhão HM et al., cited in PubMed search, 2018).

Evidence Strength — Hepatoprotective: Animal and in vitro data only. No human clinical trials have been identified.

5. Body Systems and Health Areas Associated with Simarouba

Gastrointestinal system: The leaves, bark, and seeds of this plant have been traditionally utilized to treat a variety of disorders, including fever, dysentery, malaria, and gastrointestinal disorders.
Immune and infectious disease: Antiprotozoal (antimalarial, anti-amoebic), antiviral, antibacterial, and antifungal activity have all been investigated, predominantly in vitro.
Oncology (research context): Studies have confirmed the anti-proliferative potential of the plant in colorectal, cervical, and human leukemia cancer cells.
Respiratory system: In vitro studies have demonstrated apoptotic effects in human non-small-cell lung cancer A549 cells.
Cardiovascular/hematological: The extracts are used for treating acute dysentery, fever, malaria, colitis, as a vermifuge, antimicrobial, hemostatic, and skin moisturizer.
Dermatological: Water extracts have been assessed for skin hydration, moisturization, and reduction of patchy pigmentation.
Metabolic (antidiabetic, research only): In vitro antidiabetic activity has been investigated through alpha-glucosidase inhibition assays, with results suggesting potential but requiring further study.
Liver: Preliminary hepatoprotective data exist from animal studies.

6. Dosage Forms and Dosages Reported in Studies

No standardized human dosage for Simarouba glauca extracts has been established by a pharmacopoeia or regulatory body. The following dosages have been reported exclusively in experimental research contexts:

Toxicity/safety studies (animal, oral): Test rats were orally administered aqueous extract (AESG) at doses of 500, 1000, and 2000 mg/kg body weight, respectively, daily for thirty (30) days. The data obtained indicated that the LD50 exceeded 5000 mg/kg.
Methanol extract (oral, animal): Test rats were orally administered methanol leaf extract (MESG) daily at doses of 500, 1000, and 2000 mg/kg, respectively, for thirty (30) days. The data obtained indicate that the LD50 was above 5000 mg/kg.
Seed fat (safety evaluation, animal): Acute oral toxicity and safety evaluation in a 13-week feeding trial on albino rats showed that the oil is comparable to groundnut oil in all the parameters.
In vitro anticancer dose — K562 leukemia cells: The petroleum ether extract strongly inhibited the proliferation of K562 cell lines with IC50 values of 186 µg/mL.
In vitro anticancer dose — MCF-7 breast cancer cells: The methanol extract showed significant cytotoxicity against the MCF-7 breast cancer cell line with an IC50 value of 16.12 µg/mL.
In vitro antimicrobial dose: Methanolic extract demonstrated higher antimicrobial activity with a MIC value of 3.2 mg/mL against the test pathogens.
In vitro anti-inflammatory dose: Anti-inflammatory activity assays revealed IC50 values of 328 µg/mL, 342.6 µg/mL, and 432.1 µg/mL for the aqueous, ethanol, and ethyl acetate extracts, respectively.

No human clinical trial dose has been established or published for any indication. Overall, comprehensive analysis highlights the need for further research and clinical trials to unlock the full therapeutic potential of Simarouba glauca in modern medicine.

7. Safety Considerations

Acute and Sub-Chronic Oral Toxicity (Animal Data)

A study was conducted to evaluate the toxic effect of aqueous leaf extract of Simarouba glauca (AESG) on relevant organs of male Wistar rats. The oral acute toxicity of AESG was evaluated according to the method described by Lorke. Sub-chronic toxicity was carried out in line with the guidelines of the OECD. The data obtained indicated that the LD50 exceeded 5000 mg/kg — a value conventionally associated with low acute toxicity in rodent models. The sub-chronic study examined biochemical markers of liver, kidney, and cardiac function. Liver toxicity, kidney toxicity, and heart toxicity associated with oral administration of AESG were assessed as outcome endpoints.

The belief that medicinal plants are not toxic or are with fewer side effects due to their natural origin is debatable; a study was conducted to evaluate the safety and (or) toxicity of ethanol leaf extract of Simarouba glauca (EESG) on liver, kidney, and heart functions of Wistar rats.

Quassinoid Toxicity and Seed Oil Safety

Although the seeds contain quassinoids, a toxic compound of the triterpene family, the oil is reported to be free of toxic compounds and is edible. This distinction between the seed oil (reported safe) and the whole seed or other plant extracts (which contain toxic quassinoids) is an important consideration. The fatty acid composition characteristics of the seed oil are suitable for its use as edible oil. Acute oral toxicity and safety evaluation in a 13-week feeding trial on albino rats showed that the oil is comparable to groundnut oil in all the parameters.

Cytotoxicity and Selectivity

Leaf extracts of Simarouba glauca were found to be nontoxic to lymphocytes in the leukemia cell study noted above, suggesting some degree of selectivity in the in vitro anticancer studies. However, this finding is from a single in vitro experiment and does not constitute a clinical safety determination.

Absence of Established Human Safety Data

No formal phase I human safety trial has been identified in the published peer-reviewed literature for any extract of Simarouba glauca. All toxicological data originate from animal models. The whole-plant extracts contain quassinoids that are pharmacologically potent and whose human-equivalent toxic thresholds are not established. Further research is needed to fully understand its therapeutic potential, especially regarding the identification and characterization of its active constituents.

Known Chemical Interactions — Mechanistic Considerations

Canthin-6-one has been reported to inhibit phosphorylation of the AKT kinase, and glaucarubinone targets PAK signaling pathways. Both are relevant to cellular survival and proliferation signaling cascades that overlap with pathways modulated by chemotherapy agents. Tricaproin acts as an HDAC inhibitor. These mechanistic profiles suggest the possibility of pharmacodynamic interactions with conventional oncology medications, though no clinical drug–drug interaction studies have been conducted.

8. Commercial and Industrial Forms

Seeds are economically important, as they contain 55–65% edible oil, which can be used in the manufacture of vegetable fat or margarine. This oil is also used in the manufacture of soaps, lubricants, paints, and cosmetics. Other uses of the oil are in margarines, spreads, and vanaspati. The oleine is similar to olive oil and is used in a similar way. The tree's bark, leaf, and root are encountered commercially primarily as crude or standardized extracts in powdered capsule or liquid extract form in markets where Ayurvedic and herbal preparations are sold, though no standardized pharmacopeial monograph currently governs these preparations.

Summary of Evidence Strength

The scientific literature on Simarouba glauca is substantial in terms of phytochemical characterization and in vitro bioactivity data. The phytochemical and therapeutical evaluation of S. glauca has demonstrated that the plant possesses many medicinal properties such as anticancer, anti-inflammatory, antibacterial, antimalarial, antioxidant, antifungal, antiulcer, antidiabetic, antidiarrhea, and skin moisturizer properties. However, the totality of current published evidence is preclinical. Most studies conducted earlier involved using the plant crude extract without purification and characterization, which involves critical processes in determining the essential phytochemical compounds present in the plant that have maximum activity. The path from this body of preclinical data to validated clinical use requires rigorous human trials that have not yet been conducted or reported in the accessible scientific literature.

References

Health Conditions

Health conditions that Simaruba may help support.

No conditions available.

Body Systems

Body systems that Simaruba may help support.

No body systems available.