Sacred lotus

Scientific Name(s): Nelumbo nucifera Gaertn. Family: Nymphaeaceae. 1 , 2

Common Name(s): Indian lotus , Chinese water lily , sacred lotus , kamala , padma 1 , 2

Uses

There are numerous reported pharmacologic investigations of sacred lotus, including antioxidant, hepatoprotective, immunomodulatory, anti-infective, hyperlipidemic, and psychopharmacologic activity. However, clinical trials are lacking.

Dosing

Commercial manufacturers offer sacred lotus in various dosage forms, including powder, tincture, dried petals, seeds, and leaves, and combination products in capsule form. Lotus root is also available as a health beverage and food. Cosmetic formulations are also available.

Contraindications

Avoid use if hypersensitivity exists to any constituents of sacred lotus.

Pregnancy/Lactation

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

Interactions

None well documented.

Adverse Reactions

Due to potential drug interactions, sacred lotus should be used cautiously by patients being treated for diabetes, high cholesterol, psychiatric or cardiac conditions, or erectile dysfunction.

Toxicology

No mortality or behavioral changes were observed in acute toxicity studies of an alcoholic seed extract in mice given a dose of up to 1,000 mg/kg body weight for 24 hours. The plant species may contain high levels of cadmium, copper, and lead.

Botany

N. nucifera is an aquatic plant native to eastern Asia and northern Australia. 1 , 2 , 3 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 long and 1.5 cm wide, 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. 4 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. 2 The white to pinkish flowers are solitary and range from 10 to 25 cm in diameter, 5 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 long and 0.5 to 2.5 cm in diameter, with a tough, fibrous outer layer, dense middle layer, and a spongy, inner layer. 2 , 4

History

The sacred lotus has been cultivated in eastern Asia for over 3,000 years and has been used as food and medicine, as well as 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 all over the world as a dietary staple, the plant is used ornamentally, and all parts have medicinal uses. 2

The seeds and fruits have been used in Asia to treat GI ailments (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 helpful in treating cough. 2 , 6 , 7 , 8 , 9

The leaf juice has been used to treat diarrhea, and when mixed with a leaf decoction, to treat sunstroke. The diuretic and astringent activities of the leaf extract are used to alleviate sweating and to treat fever. Medicinally, the leaves have been used to treat various bleeding conditions, including hematemesis, epistaxis, hemoptysis, hematuria, and metrorrhagia. The leaves 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. 2 , 6 , 7 , 8 , 9 , 10

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. 2 , 6 , 7 , 8 , 9

The rhizome has been used as a tonic and to treat bleeding disorders (ie, nasal bleeding, hemoptysis, hematuria, bleeding of the uterus). It 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 ring worm. 2 , 6 , 7 , 8 , 9

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. 2 , 11 , 12 , 13 , 14 , 15

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. 2 , 15 A description of the chemical composition of the seed polysaccharides is also available. 2 , 4

N -nornuciferine, O -nornuciferine, nuciferine, and roemerine are the 4 main aporphine alkaloids responsible for the pharmacological properties of the plant. 13 Numerous chemical analyses document a number of alkaloids in the leaves. 2 , 11 , 12 , 13 , 14 Several flavonoids are located in the leaves and stamens; the stamens contain kaempferol and 7 of its glycosides. 2

The starch in the rhizomes is comparable to maize and potato starch, with a fresh rhizome containing 31.2% starch. Vitamin content includes: thiamine (0.22 mg per 100 g), riboflavin (0.6 mg per 100 g), niacin (2.10 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.

Uses and Pharmacology

Numerous pharmacologic analyses have been performed on sacred lotus investigating its use as an antioxidant and hepatoprotective, as well as a treatment for diabetes, infectious disease, and hyperlipidemia. Immunomodulatory and psychopharmacologic activity have also been explored.

Antioxidant

Although the mechanism is not completely understood, antioxidant activity may be due to the presence of phenolics, alkaloids, and saponins. 6

In vitro and animal data

Four different chemical analyses document high antioxidant activity from the rhizome knot. 16 A whole rhizome extract had significant scavenging activity for small carbon-centered radicals. 16 A hydroalcoholic seed extract exhibited strong free radical scavenging activity in rats comparable with that of standard vitamin E treatment at 50 mg/kg. 6 Chemical constituents from the seed pod have lipid auto-oxidative, lipoxygenase, and free radical scavenging activity. 17 Lotus germ oil inhibited lipid peroxidation in mice liver and kidney tissues and blocked autohemolysis of mice red blood cells in a dose-dependent manner. 18 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. 18 A leaf methanol extract 19 exhibited concentration-dependent antioxidant activity against hemoglobin-induced linoleic acid peroxidation, which may be related to its flavonoid content. 20

Clinical data

No human clinical data are available regarding the antioxidant activity of sacred lotus.

Hepatoprotection
In vitro and animal 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. 21 Armepavine, an active compound in sacred lotus, has 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. 22 A dose of 300 and 500 mg/kg of lotus leaf extract in rats was comparable to 100 mg/kg of silymarin against liver-induced injury by carbon tetrachloride. 23 Hepatitis B has been treated with a combination Chinese herbal product containing sacred lotus leaf. 24

Clinical data

No human clinical data are available regarding the hepatoprotective activity of sacred lotus.

Immunomodulation
In vitro and animal data

A lotus seed ethanol extract inhibited cell-cycle progression, cytokine gene expression, and cell proliferation in human peripheral blood mononuclear cells (PBMCs). 25 ( S )-armepavine from sacred lotus immunomodulatory activity 26 , 27 includes: (1) inhibition of concanavalin A–induced splenocyte proliferation; (2) suppression of cytokine mRNA expression in splenocytes; (3) improved kidney function with reduction of immune complex deposition and glomerular hypercellularity; and (4) reduced autoantibody and T cell-mediated cytokine production in sera.

( S )-armepavine also inhibits interleukin-2 and interferon-gamma transcripts in human PBMCs without direct cytotoxicity. 26 , 27 Hydroalcoholic rhizome and seed extracts changed total and differential white blood cell counts, improved phagocytosis, and potentiated immune inflammatory reactions. 28

Clinical data

No human clinical data are available regarding the immunomodulatory activity of sacred lotus.

Infection
In vitro and animal 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. 29 Alkaloids and flavonoids from a 95% ethanol leaf extract had anti-HIV activity. 30 Antifungal activity against Candida albicans and antimalarial activity was found for various leaf constituents with no observed cytotoxicity. 31 Antibacterial activity is documented for rhizome extracts against Staphylococcus aureus , Escherichia coli , Bacillus subtilis , Bacillus pumilis , and Pseudomonus aeruginosa . 2 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 . 2

Clinical data

No human clinical data are available regarding the use of sacred lotus for treating infection.

Effects on lipids and obesity
In vitro and animal data

A Chinese herbal mixture containing sacred lotus reduced serum triglycerides and cholesterol in rats fed a high-fat diet. 32 An ethanol leaf extract stimulated lipolysis in visceral and subcutaneous adipose tissues in mice. 33 The pathway involved the beta-adrenergic receptor mediated in energy expenditure and prevention of diet-induced obesity. The ethanol leaf extract also suppressed body weight gain in mice fed a high-fat diet. 33 A flavonoid-enriched leaf extract reduced blood and liver lipids, lipid peroxidation, release of the liver enzymes AST and ALT, the LDL-C to HDL-C ratio, and lipid accumulation in the liver in a high-fat diet animal model. 34 , 35 The effect of the leaf extract on the 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. 36

Sacred lotus leaf extract has been used to treat obesity in China. The effects of the leaf extract on obesity, digestive enzymes, lipid metabolism, and thermogenesis were studied in mice induced with a high-fat diet. 37 The extract inhibited intestinal absorption of carbohydrate and lipid by inhibiting alpha-amylase and lipase; up-regulated lipid metabolism in adipocytes; prevented increases in body weight; and increased thermogenesis. An antiobesity herbal product that included sacred lotus inhibited fat accumulation by down-regulating major transcription factors in the adipogenesis pathway and lipid metabolizing enzymes utilized for accumulation of fat in adipocytes. 38

Clinical data

No human clinical data are available regarding the effects of sacred lotus on lipids and obesity.

Diabetes
Animal data

An ethanol rhizome extract reduced the blood sugar level of normal rats and glucose-fed hyperglycemic and streptozotocin-induced diabetic rats. 39 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 tolbutamide, a sulfonylurea oral hypoglycemic drug, at 73% and 67% in normal and diabetic rats, respectively. 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. 40 The mechanism of action may involve reducing release of tumor necrosis factor-alpha by activating the gamma peroxisome proliferator-activated receptor (PPAR) as well as decreasing insulin compensatory release from pancreatic islet cells. A Chinese herbal formulation decreased abnormal glucose and improved cholesterol, triglycerides, low-density lipoprotein-C (LDL-C), and high-density lipoprotein-C (HDL-C) in rats fed a high-fat diet after 4 weeks of treatment. 41 , 42 Potential mechanisms of action include inhibition of intestinal glucosidase, inhibition of lipase, and free radical scavenging activity. 41 Quercetin and glycosides in the leaves may inhibit lens aldose reductase, an enzyme associated with diabetic complications. 11 , 43

Clinical data

No human clinical data are available regarding the use of sacred lotus in diabetes.

Psychopharmacologic activity
In vitro and animal data

The alkaloids asimilobine and lirinidine, isolated from the leaves of sacred lotus, inhibited the contraction of rabbit isolated aorta induced by serotonin. 44 Neferine from lotus seed embryos may have antidepressant activity as indicated by its anti-immobility effects in mice in a forced swimming test. 45 Neferine is a direct 5-hydroxytryptamine (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. 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. 46 Sacred lotus seed extract improved scopolamine-induced dementia in rats by inhibiting acetylcholinesterase activity and inducing choline acetyltransferase expression. 47 One study documented cholinesterase inhibitory activities from sacred lotus stamen-derived compounds. 9 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 with a different mechanism. 48 Methanol rhizome extracts also have a minor sedative activity. 49 Leaf extract administered to mice attenuated induced and long-term stress and appeared to have adaptogenic activity comparable with that of diazepam. 50

Clinical data

No human clinical data are available regarding the psychopharmacologic activity of sacred lotus.

Other pharmacological effects
Allergies

A stamen methanol extract containing kaempferol inhibited key receptors and attenuated immunoglobulin E–mediated allergic reactions. 7 , 51

Antiarrhythmic effects

Neferine antagonized arrhythmias induced by aconitine in rats, calcium chloride in mice, and coronary occlusion-reperfusion in dogs. Neferine's anti-arrhythmic effect may involve blocking human-ether-à-go-go-related gene channels associated with repolarization of the cardiac action potential. 52

Antifertility effects

A petroleum ether seed extract administered to mice exhibited antiestrogenic, antiprogestational, and contraceptive activity at a dose of 3 mg/kg body weight. 53

Antipyretic

Ethanol stalk extract at 200 mg/kg reduced normal body temperature for up to 3 hours and for up to 6 hours at 400 mg/kg in rats. The activity was comparable with paracetamol. 54

Diuretic effects

A methanol rhizome extract in rats produced natriuretic and chloruretic activity. Dose-dependent effects were documented in urine volume and electrolyte excretion. 55

Erectile dysfunction activity

Neferine isolated from green seed embryo increased the concentration of cyclic adenosine monophosphate in rabbit corpus cavernosum tissue by inhibiting phosphodiesterase activity. 56 A combination Chinese herbal product containing sacred lotus seed has been used to treat sexual impotence and premature ejaculation in men. 57

GI effects

A rhizome extract was effective in reducing diarrhea in rats. 58

Uses for inflammation

A methanol rhizome extract at dosages of 200 and 400 mg/kg inhibited induced inflammation in rats. The anti-inflammatory activity was comparable with that of phenylbutazone and dexamethasone. 59 Kaempferol, isolated from sacred lotus, reduced the influx of cytokines and reactive oxygen species in aged rat gingival tissues. 60 Isoliensinine isolated from the seeds reduced bleomycin-induced pulmonary fibrosis in mice. 61 The protective effect was associated with antioxidant activity and reduced expression of inflammatory mediators.

Dosage

Most animal studies document a dosage range of 100 to 400 mg/kg, depending on which portion of the plant is used. Commercial manufacturers offer sacred lotus in various dosage forms, including powder, tincture, dried petals, seeds, and leaves, and combination products in capsule form. Lotus root is also available as a health beverage and food. 62 Sacred lotus is used cosmetically in mascara, eye shadow, lipstick, nail polish, creams, perfumes, shampoo, tonics for preventing gray hair, and tanning reagents. 63 , 64 , 65

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.

Adverse Reactions

Due to potential drug interactions, sacred lotus should be used cautiously by patients being treated for diabetes, high cholesterol, psychiatric or cardiac conditions, or erectile dysfunction.

Contraindication

Avoid use if hypersensitivity exists to any constituents of sacred lotus.

Toxicology

No mortality or behavioral changes were observed in acute toxicity studies of an alcoholic seed extract in mice up to a dose of 1,000 mg/kg body weight for 24 hours. 6 The plant species may contain high levels of cadmium, copper, and lead. 66

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