East Globe Indian Thistle, the most pronounceable name given to Sphaeranthus Indicus, is a medicine from Ayurveda that appears to have a wide variety of claims attributed to it. It appears remarkably potent at a few claims, but a huge limitation of the science behind this herb is that the mechanisms of actions and the actual molecules in the plant that exert these actions are currently not well known at all. Many studies use particular extracts of the plant to concentrate a certain class of nutrients (such as petroleum ether extracts to concentrate the nonpolar compounds like sequiterpenes), and this is as far as the evidence is currently.
It has at least once demonstrated remarkable anti-allergic effects in vitro in preventing mast cell degranulation, and has once been shown to increase testosterone levels (secondary to inhibiting conversion to DHT) with a similar potency of Finasteride. Three times it has shown efficacy in controlling Blood Glucose, with two of these studies showing similar potency to Glibenclamide (a reference drug used in the treatment of type II diabetes). One study that was in vitro on cancer cell lines noted astonishing anti-proliferative effects in the range of 80-100% inhibition, which competed with many reference drugs used in cancer therapy.
However, all of these studies are highly preliminary. East Globe Indian Thistle is at a crossroads of being amazingly promising yet not having sufficient evidence to support its usage. The lack of side-effects attributed to it may merely be secondary to it not having a large usage in society or sufficient testing.
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East Indian Globe Thistle, Mundi, Gorakhmundi, Kottakaranthai, Mahamundi
There is no human evidence at this moment in time for an optimal dose of sphaeranthus indicus, but based on rat evidence using 200mg/kg then an estimated human dose is:
Amazingly promising anti-cancer herb, which I await future research on those cancer cell lines and the bioactive that underlies these amazing effects with open arms.
Could also be a potential anti-allergic compound or testosterone booster I guess, but those are less exciting to me.
Sphaeranthus indicus (of the family Asteraceae) is an herb found mostly in southern India that has usages as a stomachic, stimulant, alterative, pectoral, demulcent, and external emollient. When used as a medicine in Ayurveda, it appears to be used in the treatment of insanity, tuberculosis, diseases of the spleen, anemia, bronchitis, elephantiasis, pain of the uterus and vagina, piles, asthma, leucoderma, and hemicrania and is commonly referred to as Gorakhmundi/Mundi (Hindi), Kottakaranthai (Tamil), or East Indian globe thistle (English) among other names.
Unlike many other plants, the flowers of Sphaeranthus appear to be commonly used (rather than root or seed oil extracts), and its growth patterns extend to Australia and Sri Lanka.
Hot water extracts (tea) of the non-flowering parts of the plant are used as an anthelminitic, as a diuretic, as a fish poison.
In a general analysis, the plant appears to be quite higher in saponin structures (5.08+/-0.2% while being low in flavonoids (0.10+/-0.11%), alkaloids (0.31+/-0.22%), phenols (0.42+/-19%), and tannins (0.6+/-0.22%) and appear to possess moderately potent antioxidant capabilities.
A preliminary study assessing 7-hdyroxyfrullanolide kinetics made note that oral administration of 50mg/kg resulted in a Cmax of 1.6μM and a half-life of 8.89h.
An ethanolic extract of Sphaeranthus Indicus at either 100, 200, or 500mg/kg orally to rats acutely with testing an hour after ingestion noted that only the 100mg/kg oral dose induced significant anxiety-reducing effects (Elevated Plus Maze) and to a lesser potency than 1mg/kg Diazepam (intraperitoneal injection; testing 30 minutes later); the two higher doses were sedative in nature, reducing locomotion. Similar effects were noted in an open-field test, and tests assessing anti-depressive effects or anti-convulsant effects of Sphaeranthus Indicus were similarly lacklustre in their results not showing any apparent differences to control.
May have weak anxiety reduction at low doses, with increasing sedative properties that may be relatively potent (lack of comparison to reference drugs); does not appear to have anti-depressive properties at these doses
A study using 300-500mg/kg ethanolic extract of the flowers of Sphaeranthus Indicus noted that the analgesic effect in a model of acetic-acid induced writhing (seen as a reliable test for pain-reducing effects in animals) noted 62.71-68.21% inhibition of writhing; this was statistically similar to 300mg/kg Aspirin (71.31%).
Possible acute pain killing effects when pre-loaded
10mg/kg Sphaeranthus indicus (petroleum ether extract) given orally to mice was found to enhance learning under scopolamine injecton (suggestive of anticholinesterase activity), although isolated compounds failed to inhibit the enzyme.
In type I diabetic mice, 200mg/kg of an ethanolic root extract of Sphaeranthus indicus appears to be effective at normalizing the body weight (which is reduced when type I diabetes is induced) with an equal efficacy to 5mg/kg Glibenclamide. Blood glucose was also reduced with both 100mg/kg and 200mg/kg, with the higher dose being equally effective as glibenclamide and the lower dose less potent. Similar effects have been noted with the alcoholic extract of the flowers, where 250-500mg/kg oral administration reduced blood glucose in type I diabetic mice over 15 days at both doses to a similar degree and was again similar to Glibenclamide at day 15 (with Glibenclamide being more effective at day 7). Glibenclamide and the herb were similar in efficacy for reducing HbA1c, with Glibenclamide being more effective at increasing glycogen content of the liver and being more effective against an acute oral glucose tolerance test where Sphaeranthus indicus was not significantly effective.
In dexamethasone-induced insulin resistant mice (1 week of 1mg/kg intramuscular injections), Sphaeranthus indicus methanolic extract was able suppress the increase in glucose and triglycerides in a dose-dependent manner. When compared to ketoconazole (24mg/kg) and pioglitazone (2mg/kg), 400mg/kg Sphaeranthus indicus was equally effective in normalizing glucose and triglycerides as ketoconazole while 800mg/kg was needed to be equal to pioglitazone. In isolated hemidiaphragms to assess glucose uptake, Sphaeranthus indicus was able to encourage glucose uptake in insulin free and insulin stimulated conditions while pioglitazone was only effective in insulin-stimulated conditions. 
Seemingly potent effects in diabetic animals for reducing blood glucose, but the mechanisms are not currently elucidated; effects may be related to the immune system. Has only once been tested in an acute oral glucose tolerance test and has seemingly failed to influence serum glucose in this instance
Secondary to its 5α-reductase inhibitory properties (nearing Finasteride in potency), the petroleum and ethanolic extracts of Sphaeranthus Indicus at 50mg/kg were able to increase testosterone to similar levels as Finasteride over 28 days; reaching approximately 10ng/mL in rats from a baseline value of 1-2ng/mL.
7-hydroxyfrullanolide, extracted from flower heads, was able to attenuate pro-inflammatory cytokines release from stimulated PBMCs with IC50 values of 0.8μM and 1.4μM for TNF-α and IL-6 with cytotoxicity not being apparent below 100uM; similar potency was observed in synovial cells extracted from persons with Rheumatoid Arthritis, with IC50 values of 1μM for both TNF-α and IL-6.
General anti-inflammatory effects, which require relatively low concentrations and may be practically relevant following oral administration
One study has noted that with 150-300mg/kg of the ethyl acetate and ethanolic fractions, Mast Cell degranulation was suppressed 77–86% in a sheep serum model and 77–88% when cells were incubated with compound 48/80; both of these tests were more potent than the reference drug ketotifen fumarate (75% and 69%, respectively, at 1-100mg/kg). The petroleum ether and water extracts were also effective, but to a lesser degree.
Possibly potent anti-allergic effects by preventing degranulation of mast cells, with more efficacy than Ketotifen
Oral ingestion of the petroleum ether extract to mice noted that macrophage phagocytic activity is enhanced in a relatively dose dependent manner up to 400mg/kg (with only 300-400mg/kg being statistically significant) and that only 200mg/kg was effective in increasing the humoral response to SRBCs, with 50-100mg/kg and 300-400mg/kg trending to be effective but not significantly so.
That being said, the extracts of Sphaeranthus indicus have once been found to preserve the humoral response in the presence of Cyclophosphamide; normally suppressive.
May have immunomodulatory properties, but no real indicative of practical relevance or potency relative to other compounds
A basic ethanolic extract of the flowers at 300-500mg/kg was given orally to rats which resulted in 42.66% and 50.5% inhibition of carrageenan-induced paw edema (a biomarker of inflammation) when measured at 1 hour and showed efficacy for the 7 hours under measurement; it was not significantly different than 300mg/kg Aspirin, although it trended to be less potent.
Oral administration of 7-HF to mice at 25, 50, and 75mg/kg was able to suppress TNF-α and IL-6 release in LPS-stimulated mice by 53-86% and 29-59% respectively; acting in a dose-dependent manner; in a septic shock test, 50mg/kg 7-HF was as protective as Dexamethasone. In chronic inflammation tests, 100mg/kg 7-HF was as potent as Dexamethasone at attenuating the pathology of colitis, collagen-induced arthritis, and edema.
Interventions in animals following oral administration of Sphaeranthus Indicus appear to establish potent effects of isolated 7-HF and the ethanolic extract; similar to reference drugs
Note on this section, currently the study establishing most apoptosis of cancer cells (seemingly potent) failed to establish what dose is required to kill healthy cells and did not use a control; take the info with a grain of salt
Lung A-549 cells have been shown to have their growth inhibited at 100ug/mL concentration of Sphaeranthus Indicus aqueous (78%), petroleum ether (92%), and ethanolic (81%) extracts; outperforming 10uM Paclitaxel (69%).
Prostatic DU145 and PC3 cells have been shown to have their growth inhibited at 100ug/mL concentration of Sphaeranthus Indicus aqueous (55% and 30%), petroleum ether (98% both cell lines), and ethanolic (61% and 43%) extracts; both outperforming 1uM mitomycin C (51-54%).
Appears to significantly attenuate cell proliferation, which may be related to induction of apoptosis
These three extracts have also been tested in a model of Benign Prostatic Hyperplasia (not inherently cancerous) in rats, and increasing doses (10, 20, 50mg/kg oral ingestion) of these three extracts was given alongside 3mg/kg testosterone and compared to 1mg/kg Finasteride. While Finasteride attenuated the increase in prostatic weight to 19.9% of control, the highest dose of the most effective extract (petroleum ether) attenuated this increase to 26.62% and was deemed to not be significantly different; the higher doses of the aqueous and ethanolic extract suppressed growth to 39.99% and 55.83% of control respectively. A subsequent reduction in PSA levels was noted to be similar as Finasteride as well.
When tested in vitro, the IC50 of the petroleum extract in inhibiting 5α-Reductase was 0.132mg/mL which was more effective than the water (0.387mg/mL) and ethanolic (0.317mg/mL) extracts but less than Finasteride (1.06mcg/mL).
Appears to possess 5α-Reductase inhibitory potential
Neuroblastoma IMR32 cells have been shown to have their growth inhibited at 100ug/mL concentration of Sphaeranthus Indicus aqueous (66%), petroleum ether (99%), and ethanolic (71%) extracts; outperforming Adriamycin at 1uM (70%).
Breast MCF-7 cells have been shown to have their growth inhibited at 100ug/mL concentration of Sphaeranthus Indicus aqueous (40%), petroleum ether (94%), and ethanolic (34%) extracts; outperforming 1uM Adriamycin (75%).
Colorectal CoLo-205 cells have been shown to have their growth fully (100%) inhibited at 100ug/mL concentration of Sphaeranthus Indicus in vitro with the petroleum extract, with aqueous and ethanolic extracts wholly ineffective. This significantly outperformed 20uM 5-Flurouracil (54%), and in HL-60 cells the IC50 was determined to be 53ug/mL.
HL-60 was chosen to elucidate the mechanisms of the petroleum extract of Sphaeranthus Indicus, and it was found to induce DNA laddering and apoptosis, and increasing concentrations (10, 30, 100ug/mL) increased the G0 cell population to 4% to 10% and 80% higher than control. Cell death appears to be apoptotic rather than necrotic and is mediated by a loss of mitochondrial membrane potential (the degree of caspase 3, 8, and 9 release correlating the cell population in G0 phase).
Isolated 7-Hydroxyfrullanolide was able to inhibit proliferation of Leukemic THP-1 cells at 50-100uM concentration (24-47%) with no effect at 10uM; underperforming 20uM 5-Fluorouracil (72%).
Ovarian IGR-OV-1 cells have failed to have their growth significantly inhibited at 100ug/mL concentration of Sphaeranthus Indicus.
150-300mg/kg of the ethanolic extract of Sphaeranthus Indicus alongside 12mg/kg Cisplatin in rats for 10 days (after 6 days of Cisplatin only treatment) was able to effectively normalize GSH and MDA in renal tissue, both of which were altered with Cisplatin in isolation and both Creatinine and Urea were almost normalized. Ingestion of the extract in isolation did not result in any significant differences relative to control, and histopathological analysis appeared to revert acute tubular necrosis (seen with 6 days of Cisplatin) back to near-similar morphology.
Preliminary evidence suggests that Sphaeranthus Indicus is highly renoprotective
Oral doses of up to 2000mg/kg of Sphaeranthus Indicus petroleum ether extract and ethanolic root extract are not associated with toxicity for up to 2 weeks of usage, and 4000mg/kg of the methanolic extract has been tested and observed for 48 hours with no apparent acute toxicity.
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