Sacred Lotus

Scientific Name(s): Nelumbo nucifera Gaertn.
Common Name(s): Chinese water lily, Indian lotus, Kamala, Lotus plumule, Padma, Sacred lotus

Medically reviewed by Drugs.com. Last updated on Jun 1, 2022.

Clinical Overview

Use

Sacred lotus has been investigated (primarily in vitro and in animal studies) for various activities, including antioxidant, hepatoprotective, immunomodulatory, anti-infective, hyperlipidemic, and psychopharmacologic. However, clinical trial data are lacking to recommend use for any indication.

Dosing

Clinical trials are lacking to provide dosing recommendations for sacred lotus.

Contraindications

Avoid use if hypersensitivity exists to any constituents of sacred lotus. A case of anaphylactic reaction has been reported.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Due to potential for drug interactions, sacred lotus should be used cautiously in individuals receiving treatment for diabetes, high cholesterol, psychiatric or cardiac conditions, or erectile dysfunction.

Toxicology

No data. The plant species may contain high levels of cadmium, copper, and lead.

Scientific Family

• Nymphaeaceae (lotus lily)

Botany

N. nucifera is an aquatic plant native to eastern Asia and northern Australia.(Kreunen 1999, Masuda 2006, Mukherjee 2009) The plant has long stems with leaves and flowers, requires plenty of space and sun, and grows up to 5.7 m in height. The ovoid fruit is a collection of indehiscent nutlets growing 1 m in length and 1.5 cm in width, with a brown to black pericarp. The seeds fill the innermost portion of the flower. The chemical composition of the fruit wall and seed coat enhances the longevity of the fruits.(Van Bergen 1997) The leaves are either aerial and cup-shaped or floating and flat, with the aerial leaves ranging from 24 to 33 cm in length, and the floating leaves ranging from 23 to 30 cm. The leaves are large in diameter, ranging from 20 to 90 cm.(Mukherjee 2009) The white to pinkish flowers are solitary and range from 10 to 25 cm in diameter,(Li 2009b) with sepals, petals, and stamens grouped in a spiral pattern. The sacred lotus is the national flower of India and is cultivated for its elegant scent. The white to yellowish brown rhizome is 60 to 140 cm in length and 0.5 to 2.5 cm in diameter, with a tough, fibrous outer layer, dense middle layer, and spongy, inner layer.(Mukherjee 2009, Van Bergen 1997) A synonym of N. nucifera is Nelumbinis plumula.

History

The sacred lotus has been cultivated in eastern Asia for more than 3,000 years and has been used medicinally, as food, and in religious and cultural activities. The Egyptians worshiped the flowers, fruits, and sepals of the plant, commonly found along the banks of the Nile River. In addition to being consumed throughout the world as a dietary staple, the plant is used ornamentally, and all parts have medicinal uses.(Mukherjee 2009) Sacred lotus has also been used as an ingredient in cosmetics.(Kim 2015)

The seeds and fruits have been used in Asia to treat GI conditions (eg, poor digestion, enteritis, chronic diarrhea), insomnia, cardiovascular disease (eg, heart palpitations, hypertension, arrhythmia), nervous disorders, skin conditions (eg, dermatopathy, leprosy, tissue inflammation), halitosis, cancer, and high fevers; as an antiemetic, poison antidote, and diuretic; and in men's health (eg, spermatorrhea) and women's health (ie, leucorrhea, menorrhagia). The seeds have also been used for hemostasis function. Honey mixed with the seed powder is reputedly useful in treating cough.(Jung 2010, Liao 2008, Mukherjee 2009, Rai 2006, Shim 2009)

The leaf juice has been used to treat diarrhea, and when mixed with a leaf decoction, to treat sunstroke. Alleviation of sweating and fever has been attributed to the diuretic and astringent activities of the leaf extract. Medicinally, the leaves have been used to treat various bleeding conditions, including hematemesis, epistaxis, hemoptysis, hematuria, and metrorrhagia. The leaves and leaf extract have also been used to treat obesity and hyperlipidemia. The stem has been used in traditional Ayurvedic medicine as an anthelmintic and to treat strangury. Lotus leaf is a major ingredient of antioxidant beverages and teas in China, with annual production exceeding 800,000 tons.(Huang 2010a, Jung 2010, Liao 2008, Mukherjee 2009, Ono 2006, Rai 2006, Shim 2009)

Sacred lotus flowers have traditionally been used to treat various bleeding disorders, cholera, fever, vascular disorders of the liver, hyperdipsia, and abdominal cramps, and as a cardiac tonic. Eye infections have been treated with lotus honey.(Jung 2010, Liao 2008, Mukherjee 2009, Rai 2006, Shim 2009)

The rhizome has been used as a tonic and to treat bleeding disorders (ie, nasal bleeding, hemoptysis, hematuria, bleeding of the uterus) and is included in Chinese herbal formulations to treat cancer, chronic liver cirrhosis, and tissue inflammation. Hemorrhoids, dysentery, and dyspepsia have been treated with powdered formulations of the rhizome. An external paste formulation has been effective in treating scabies and ringworm.(Jung 2010, Liao 2008, Mukherjee 2009, Rai 2006, Shim 2009)

Chemistry

Pharmacologically active constituents have been isolated from the seed, leaf, flower, and rhizome. The chemical constituents include alkaloids, steroids, triterpenoids, flavonoids, glycosides, and polyphenols, as well as a variety of minerals.(Kunitomo 1973, Lim 2006, Luo 2005, Mukherjee 2009, Nishibe 1986, Zheng 2010)

The seeds are rich in protein, amino acids, unsaturated fatty acids, minerals, starch, and tannins. Numerous alkaloids are the major secondary metabolites in the seeds.(Mukherjee 2009, Nishibe 1986) A description of the chemical composition of the seed polysaccharides is also available.(Mukherjee 2009, Van Bergen 1997)

N-nornuciferine, O-nornuciferine, nuciferine, and roemerine are the 4 main aporphine alkaloids responsible for the pharmacological properties of the plant.(Luo 2005) Numerous chemical analyses document a number of alkaloids in the leaves.(Kunitomo 1973, Lim 2006, Luo 2005, Mukherjee 2009, Zheng 2010) Several flavonoids are located in the leaves and stamens; the stamens contain kaempferol and 7 of its glycosides.(Mukherjee 2009) Higenamine, liensinine, dauricine, isoliensinine, neferine, and nuciferine are found in the green embryo of lotus seeds (known as lotus plumule or N. plumula) and exhibit high bioactivity. In 2017, higenamine was added to the World Anti-Doping Agency’s prohibited list as a nonselective beta-2 agonist.(Yang 2021, Yen 2020)

The starch in the rhizomes is comparable with maize and potato starch, with a fresh rhizome containing 31.2% of starch. Vitamin content includes the following: thiamine 0.22 mg per 100 g, riboflavin 0.6 mg per 100 g, niacin 2.1 mg per 100 g, and ascorbic acid 1.5 mg per 100 g. An asparagine-like amino acid (2%) has also been isolated in the rhizomes.(Mukherjee 2009)

Uses and Pharmacology

Numerous pharmacologic analyses of sacred lotus have been performed to investigate use as an antioxidant and hepatoprotective, as well as a treatment for diabetes, infectious disease, and hyperlipidemia. Immunomodulatory and psychopharmacologic activities have also been explored.

Antiarrhythmic effects

Animal data

Neferine antagonized arrhythmias induced by aconitine in rats, by calcium chloride in mice, and by coronary occlusion-reperfusion in dogs. Neferine's antiarrhythmic effect may involve blocking human-ether-à-go-go–related gene channels associated with repolarization of the cardiac action potential.(Gu 2009)

Antifertility effects

Animal data

In mice, antiestrogenic, antiprogestational, and contraceptive activities were observed with a petroleum ether seed extract dose of 3 mg/kg body weight.(Mazumder 1992)

Antifungal/Antibacterial activity

In vitro data

Antifungal activity (against Candida albicans) and antimalarial activity of various leaf constituents have been observed, with no cytotoxicity.(Agnihotri 2008) A rhizome extract had antifungal and antiyeast activity comparable with griseofulvin against 5 different strains of fungi and yeast, including C. albicaus, Aspergillus niger, Aspergillus fumigatus, and Trichophytum mentagopyhtes.(Mukherjee 2009) Antibacterial activity has been documented for rhizome extracts against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Bacillus pumilis, and Pseudomonas aeruginosa.(Mukherjee 2009) The leaf extract demonstrated anticariogenic activity most effectively against Streptococcus anginosus and least effectively against Streptococcus oralis, with actions against Streptococcus sobrinus, Fusobacterium nucleatum, Streptococcus mutans, Streptococcus gordonii, Streptococcus criceti, and Streptococcus ratti falling somewhere in between.(Lee 2019)

Antioxidant activity

Although the mechanism is not completely understood, antioxidant activity may be due to the presence of phenolics, alkaloids, and saponins.(Rai 2006)

Animal and in vitro data

Four different chemical analyses document high antioxidant activity of the N. nucifera rhizome knot. A whole rhizome extract had significant scavenging activity for small carbon-centered radicals.(Hu 2002) A hydroalcoholic seed extract exhibited strong free radical scavenging activity in rats comparable with that of standard vitamin E treatment at 50 mg/kg.(Rai 2006) Chemical constituents from the seed pod have lipid auto-oxidative, lipoxygenase, and free radical scavenging activity.(Ling 2005) Lotus germ oil inhibited lipid peroxidation in mouse liver and kidney tissues and blocked autohemolysis of mouse red blood cells in a dose-dependent manner.(Li 2009b) High antioxidant activity was also found in the germ oil in a lipid system (ie, lard peroxidation). The phenolic compounds and tocopherols may contribute to the antioxidant activity of lotus germ oil.(Li 2009b) A leaf methanol extract(Wu 2003) exhibited concentration-dependent antioxidant activity against hemoglobin-induced linoleic acid peroxidation, which may be related to its flavonoid content.(Lin 2009a) The highest antioxidant activity has been demonstrated in vitro with extracts from the stamen, with respective decreasing activity found in old leaf, seed embryo, petal, flower stalk, and then leaf stalk.(Temviriyanukul 2020)

Antipyretic effects

Animal data

In rats, ethanol stalk extract 200 mg/kg reduced normal body temperature for up to 3 hours and for up to 6 hours at 400 mg/kg, activity that was comparable with paracetamol.(Sinha 2000)

Antiviral activity

Animal and in vitro data

Ethanol seed extracts inhibited herpes simplex virus type 1 (HSV-1) multiplication in HeLa cells without cytotoxicity by inhibiting gene expression of HSV-1.(Kuo 2005) Alkaloids and flavonoids from ethanol leaf 95% extract had anti-HIV activity.(Kashiwada 2005)

Anti-inflammatory effects

Animal and in vitro data

A methanol rhizome extract at dosages of 200 mg/kg and 400 mg/kg inhibited induced inflammation in rats. The observed anti-inflammatory activity was comparable with that of phenylbutazone and dexamethasone.(Mukherjee 1997a) Kaempferol, isolated from sacred lotus, reduced the influx of cytokines and reactive oxygen species in aged rat gingival tissues.(Kim 2007) Isoliensinine isolated from the seeds reduced bleomycin-induced pulmonary fibrosis in mice, a protective effect associated with antioxidant activity and reduced expression of inflammatory mediators.(Xiao 2005)

In orbital fibroblasts derived from patients with Graves disease, neferine suppressed interleukin 13 (IL-13)–induced autophagy by upregulating nuclear factor erythroid 2–related factor 2 (antioxidant pathway) as well as IL-13–induced inflammation and adipocyte differentiation.(Li 2021) In an atopic dermatitis mouse model, neferine 3 mg/kg reduced symptoms related to inflammation, producing a response similar to that of dexamethasone 0.2 mg/kg. Inhibition of inflammation and swelling of the spleen was also documented.(Yang 2021)

Diabetes

The mechanism of action in parameters of diabetes may involve reducing release of tumor necrosis factor alpha by activating the gamma peroxisome proliferator–activated receptor as well as decreasing insulin compensatory release from pancreatic islet cells.(Pan 2009) Quercetin and glycosides in the leaves may inhibit lens aldose reductase, an enzyme associated with diabetic complications.(Jung 2008, Lim 2006)

Animal data

An ethanol rhizome extract reduced the blood sugar level of normal rats and glucose-fed hyperglycemic and diabetic (streptozotocin-induced) rats. In normal rats, the rhizome extract improved glucose tolerance and increased the effectiveness of injected insulin. The activity of the extract was comparable with that of the sulfonylurea oral hypoglycemic drug tolbutamide (ie, at 73% and 67% that of tolbutamide in normal and diabetic rats, respectively).(Mukherjee 1997b) Neferine, isolated from the green seed embryo, was comparable with rosiglitazone in enhancing insulin sensitivity and improving fasting blood glucose, triglycerides, and inflammatory cytokines in insulin-resistant rats.(Pan 2009)

Diuretic effects

Animal data

A methanol rhizome extract in rats produced natriuretic and chloruretic activity. Dose-dependent effects were documented in urine volume and electrolyte excretion.(Mukherjee 1996a)

Erectile dysfunction

In vitro data

Neferine isolated from green seed embryo increased the concentration of cyclic adenosine monophosphate in rabbit corpus cavernosum tissue by inhibiting phosphodiesterase activity.(Chen 2008)

GI effects

Animal data

A rhizome extract was effective in reducing diarrhea in rats.(Talukder 1998)

Hepatoprotective effects

Animal and in vitro data

Ethanol seed extracts exhibited hepatoprotective effects against production of serum enzymes and cytotoxicity caused by carbon tetrachloride. The extract also protected against the genotoxic and cytotoxic effects of aflatoxin B1.(Sohn 2003) Armepavine, an active compound in sacred lotus, has shown antifibrotic effects in rats by activating the anti–NF-kappaB pathway. Armepavine yielded better results compared with silymarin (ie, milk thistle) in reducing certain metabolic parameters in hepatic fibrosis.(Weng 2009) In rats, lotus leaf extract doses of 300 mg/kg and 500 mg/kg were comparable with silymarin 100 mg/kg against liver-induced injury by carbon tetrachloride.(Huang 2010b)

Hyperlipidemia

Animal and in vitro data

In a high-fat diet animal model, a flavonoid-enriched leaf extract produced reductions in blood and liver lipids, lipid peroxidation, release of the liver enzymes AST and ALT, LDL cholesterol to HDL cholesterol ratio, and lipid accumulation in the liver.(Lin 2009b, Wu 2010) The effect of the leaf extract on high-fat–induced lipid metabolic disorder was comparable with results of silymarin and simvastatin treatment. The flavonoids from the leaf extract may exert antiatherogenic properties by inhibiting vascular smooth muscle cell proliferation and migration.(Ho 2010)

Immunomodulatory effects

Animal and in vitro data

A lotus seed ethanol extract inhibited cell-cycle progression, cytokine gene expression, and cell proliferation in human peripheral blood mononuclear cells (PBMCs).(Liu 2004) The immunomodulatory activity of (S)-armepavine from sacred lotus includes the following: inhibition of concanavalin A–induced splenocyte proliferation; suppression of cytokine mRNA expression in splenocytes; improved kidney function with reduction of immune complex deposition and glomerular hypercellularity; and reduced autoantibody and T-cell–mediated cytokine production in sera.(Liu 2006, Liu 2007)

(S)-armepavine also inhibits IL-2 and interferon-gamma transcripts in human PBMCs without direct cytotoxicity.(Liu 2006, Liu 2007) Hydroalcoholic rhizome and seed extracts altered total and differential white blood cell counts, improved phagocytosis, and potentiated immune inflammatory reactions.(Mukherjee 2010)

A stamen methanol extract containing kaempferol inhibited key receptors and attenuated immunoglobulin E–mediated allergic reactions.(Shim 2009, Toyoda 1997)

Obesity

Animal data

The effects of the leaf extract on obesity, digestive enzymes, lipid metabolism, and thermogenesis were studied in mice with high-fat diet–induced obesity. The extract inhibited intestinal absorption of carbohydrates and lipids by inhibiting alpha-amylase and lipase; upregulated lipid metabolism in adipocytes; prevented increases in body weight; and increased thermogenesis.(Ono 2006)

Clinical data

In overweight Chinese participants with a body mass index between 23 and 30 kg/m² enrolled in a double-blind, randomized, controlled trial, administration of a N. nucifera leaf extract beverage significantly reduced body fat, waist circumference, and visceral fat in men. Visceral fat was reduced by 6.5% and 9.4% (P=0.037, P=0.023) at weeks 6 and 12, respectively, with the 2 g/day dose. In women, body fat also significantly decreased by 10.5% (P=0.009) and by 8.6% (P=0.027) by week 12; however, no significant changes were observed in visceral fat or waist or hip circumference, possibly due to the lower ratio of visceral fat in women participants relative to that in men.(Ye 2021)

Osteoporosis

Animal data

In a postmenopausal (ovariectomized-induced) osteoporosis mouse model, neferine treatment for 4 weeks resulted in dose-dependent and significant improvements in bone volume and increases in serum alkaline phosphatase.(Chen 2019)

Photoaging effects

In vitro data

Antiphotoaging properties have been demonstrated with lower concentrations of neferine (ie, 0.2 mcM, 0.4 mcM, 0.8 mcM) in an in vitro model using human dermal fibroblasts. In contrast, at higher concentrations, neferine caused cell apoptosis and death.(Khan 2021)

Psychopharmacologic activity

Animal and in vitro data

The alkaloids asimilobine and lirinidine, isolated from the leaves of sacred lotus, inhibited serotonin-induced contraction of rabbit isolated aorta.(Shoji 1987) Neferine from lotus seed embryos may have antidepressant activity, as indicated by its anti-immobility effects in mice in a forced swimming test.(Sugimoto 2010) Neferine is a direct 5-hydroxytryptamine 1A (5-HT_1A) receptor agonist and may inhibit 5-HT reuptake or activation of 5-HT metabolism. The antidepressant effect was comparable with that of maprotiline and imipramine. Allantoin and neferine from the N. nucifera rhizome significantly improved neurogenesis and depressive symptoms in an irradiation-induced depression model in vivo.(Kang 2018)

In mice, a methanol rhizome extract may improve learning and memory by enhancing neurogenesis through increased cell proliferation and cell differentiation in the dentate gyrus of the hippocampus.(Yang 2008) Sacred lotus seed extract improved scopolamine-induced dementia in rats by inhibiting acetylcholinesterase activity and inducing choline acetyltransferase expression.(Oh 2009) One study documented cholinesterase inhibitory activities from sacred lotus stamen-derived compounds.(Jung 2010) In vitro, flower and leaf stalk extracts have been observed to have high inhibitory activity against key enzymes relevant to Alzheimer disease (ie, acetylcholinesterase, butyrylcholinesterase, beta-secretase).(Temviriyanukul 2020)

Methanol seed extracts containing neferine inhibited locomotor activity at 50 mg/kg and elicited potent effects at 100 mg/kg. Neferine induced sedation, hypothermia, antifever effects, and anxiolytic effects comparable with those of diazepam but via a different mechanism.(Sugimoto 2008) Methanol rhizome extracts also have a minor sedative activity.(Mukherjee 1996b) Leaf extract administered to mice attenuated induced and long-term stress and appeared to have adaptogenic activity comparable with that of diazepam.(Kulkarni 2008)

Dosing

Clinical trials are lacking to provide dosing recommendations for sacred lotus. Various formulations are available commercially, including powder, tincture, dried petal, seed, and leaf preparations, and combination products (eg, in capsule form).

Hygenamine misuse: Consumption of lotus plumule products was shown to produce higenamine levels that reached the "adverse analytical findings" criterion for doping according to the World Anti-Doping Agency. Within 3 hours of consuming lotus plumule extract powder that contained 679.6 mcg of higenamine per dose, urine specimens in 4 of 6 participants reached the positivity criterion of 10 ng/mL. Urinary concentrations of higenamine increased over the 3-day regimen.(Yen 2020)

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Sacred lotus may interact with drugs used to treat diabetes, liver conditions, and infections, as well as with lipid-lowering, psychotropic, cardiac, or erectile dysfunction medications.

The glucose-lowering effect of metformin was reduced in mice with coadministration of nuciferine. A concentration-dependent reduction in the hepatic intracellular accumulation of metformin was demonstrated in vitro and in vivo. The mechanism involved inhibition of the organic cation transporter 1 and multidrug and toxin extrusion 1 hepatic enzymes.(Li 2018)

Adverse Reactions

Due to potential drug interactions, sacred lotus should be used cautiously in individuals receiving treatment for diabetes, high cholesterol, psychiatric or cardiac conditions, or erectile dysfunction.

Avoid use if hypersensitivity exists to any constituents of sacred lotus. A case of anaphylactic reaction has been reported.(Nishimura-Tagui 2020)

Toxicology

In acute toxicity studies in mice, no mortality or behavioral changes were observed with an alcoholic seed extract at a dose up to 1,000 mg/kg body weight for 24 hours.(Rai 2006) The plant species may contain high levels of cadmium, copper, and lead.(Ebrahimpour 2008)

In 2017, higenamine was added to the World Anti-Doping Agency's prohibited list as a nonselective beta-2 agonist.(Yang 2021, Yen 2020)

References

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