Phytopharmaceutical Formulations and Other Uses of Moringa oleifera

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Phytopharmaceutical Formulations and Other Uses of Moringa oleifera

This entry is adapted from the peer-reviewed paper 10.3390/ijms24032098

Moringa oleifera, also known as the “tree of life” or “miracle tree,” is classified as an important herbal plant due to its immense medicinal and non-medicinal benefits. The plant is used to cure wounds, pain, ulcers, liver disease, heart disease, cancer, and inflammation.

Moringa oleifera plant uses Phytopharmaceutical formulations nanoparticles

1. Taxonomical Classification

The plant M. oleifera belongs to the Kingdom: Plantae; Sub kingdom: Tracheobionta; Super division: Spermatophyta; Division: Magnoliophyta; Class: Magnoliopsida; Sub class: Dilleniidae; Order: Capparales; Family: Moringaceae; Genus: Moringa; Species: oleifera ^[1]^[2]^[3].

2. Morphology

The tree grows rapidly in loamy and well-drained sandy soils, preferring a height of 500 m above sea level ^[4]. Normally, the tree is small to medium in size, the leaves are naturally trifoliate, the flowers are born on an inflorescence 10–25 cm long ^[3], and the fruits are usually trifoliate and commonly referred to as “pods” ^[1]. The trunk usually grows straight but is occasionally poorly formed, the branches are usually disorganized, the canopy is umbrella-shaped; the brown seeds have a semi-permeable hull, and each tree has a capacity of about 15,000–25,000 seeds per year ^[5].

3. Phytopharmaceutical Formulations

Plant extracts have always attracted researchers’ attention for producing various pharmaceutical products. This process usually involves the production of medicinal products characterized by two things: first, the production of a stable product, and second, patient compliance. The advantage of Moringa plant extracts is that it appears to be exceedingly safe at the doses and in the amounts commonly utilized for therapeutic efficacy ^[6]. M. oleifera has been widely accepted in the research area, and scientists have used an array of approaches to develop various formulations. The various phytoformulations prepared using M. oleifera are tabulated below (Table 1).

Table 1. Phytopharmaceutical formulations prepared using M. oleifera extract.

Plant Part Used	Nature of Extract	Formulation	Method of Preparation and Polymers/Excipients Used	Application	Inference	References
Leaves	Ethyl acetate	Polyherbal formulation	Suspending method (carboxy methyl cellulose)	Anti-ulcer	The potent anti-ulcer activity was observed in polyherbal formulations.	^[7]
Leaves	Aqueous/methanolic	Polyherbal ointments	Water in oil mixing (wool fat, hard paraffin, cetostearyl alcohol, PEG4000, PEG400, sorbitol mono-oleate, liquid paraffin, white beeswax, span 60, tween 60)	Edema	The methanolic extract had a more anti-inflammatory effect than the aqueous extract. Apart from potent anti-inflammatory activity, the -miscible base ointment showed good drug diffusion.	^[8]
Seed	Oil	Micro-dispersion	Vortexing (Span 80, tween 80)	Anti-inflammatory	Showed higher permeation rather than pure oil. Tween 80 enhances the permeation.	^[9]
Leaves	Ethanolic	Lozenges	Wet granulation (Polyvinyl-pyrrolidone, magnesium stearate, menthol, vanillin)	Anti-microbial activity	Flavoring agents gave better acceptance for the consumer than formulation with no addition of flavoring agent. Due to limited solubility of quercetin in aq. phase, only 40–50% of quercetin is released.	^[10]
Seed	Oil	Nano-micelle	Microemulsion method (Tween 80, Ethanol)	Mitochondrial cancer cell apoptosis	Targetability increases when seed oil is formulated in nano-micelle. Nanomicelles kill 50% colon cancerous Caco-2 cells compared to seed oil which kills only 40% of cancer cells.	^[11]
Leaves + fruits (Embelia ribes)	Hydro-alcoholic	Thermo-reversible in-situ nasal gel	Cold method (poly (ethylene glycol) (PEG400), Pluronic F127, xanthum gum, carbopol 934), hydroxypropyl methylcellulose (HPMC K4M).	Allergic rhinitis	On increasing PF127 concentration, the viscosity of in-situ gel increases. PF127 exhibited less mucoadhesion as compared to HPMC/carbopol/xanthan gum. Plant in situ gel was formulated to overcome low bioavailability and first-pass metabolism.	^[12]
Leaves	Aqueous, ethanolic	Film dressing	Solvent casting method (Alginate, pectin)	Wound healing	Aq. leaf extracts showed effective results in cell proliferation and migration properties. Optimal physicochemical properties were exhibited by the extract.	^[13]
Leaves	Ethanolic	Effervescent tablets	Wet granulation (70% ethanol, lactose, citric acid, tartaric acid, sodium bicarbonate, aspartame, PEG600)	Anti-anemia	The effervescent times of all formulations were less than 2 min, and thus all lie within the range mentioned in the pharmacopoeia standard.	^[14]
Seed	Oil	Anti-inflammatory cream	Triturating process (Oleic acid, sodium hydroxide, potassium hydroxide, aluminum hydroxide, liquid ammonia, sodium benzoate).	Anti-inflammatory	Optimized formulation showed 60% inhibition, whereas the standard inhibited 65% protein denaturation. Oil reduced paw edema by 64%, whereas formulation reduced it by 70%.	^[15]
Leaves		Silver NPs (AgNPs)	Shaking method (Silver nitrate)	Anti-fungal activity	ZOI increases with an increase in the concentration of AgNPs against Candida albicans. The agar plate distributed with the highest concentration of AgNPs exhibited lowest cultural population.	^[16]
Leaves	Aqueous	Hydrocolloid film dressing	Solvent casting method (sodium alginate, pectin)	Wound healing in diabetic condition	Hydrocolloid dressing is free of any irritants or toxic substances. 0.5% and 0.1 % film dressing converts to gel after being exposed to wounds compared to 1% due to rapid gelation.	^[17]
Leaves	Hydro-alcoholic	In-situ gel	Cold technique (Pluronic F127, gellan gum, glycerine, Carbopol 934)	Allergic rhinitis	Dose-dependent results of the prepared formulation were seen in mice induced with ova albumin along with a significant decrease in Ig E levels.	^[18]
Leaves	Aqueous	Nanofibers impregnated onto Hydrocolloid film	Electrospinning (poly-(ethylene oxide) (PEO), sodium alginate, pectin, glycerol)	Chronic Wound dressing	PEO concentrations and nanofiber diameter were directly proportional. Polymers in low concentration lead to poor entanglement of chain and produce beads or lumps of nanofibers and also form discontinuous fibers. At very high concentrations, the electrospinning stainless needle gets blocked, and polymer ejection gets obstructed. Electrospinning time increases, and the release of bioactive from film increases.	^[19]
Leaves	Aqueous/Ethanolic	Silver nanoparticle loaded Composites	Sodium hypophosphite, silver nitrate, citric acid, Kaolin (clay), Chitosan (LMW), sodium carbonate.	Anti-oxidant	Ethanolic extract proved to be a better composite as compared to aqueous extract. ZOI is higher with alcoholic extract than the aqueous extract. Fabrics with AgNPs composites showed excellent UV protection than clay composites.	^[20]
Leaves	Hydro-alcoholic	Polymeric microparticles (MPs)	Spray dried method (Chitosan)	Exuding wound treatment	Decreasing the extract amount increases the entrapment efficiency. Unloaded MPs have wrinkled surfaces, whereas extract-loaded MPs have spherical and smooth surface. The gel produces a covering layer that protects the wound because of chitosan.	^[21]
Leaves	Aqueous	Iron oxide nanorods	Mixing method (Iron (III) chloride hexahydrate)	Anti-bacterial property	Nanoparticles formed showed concentration-dependent inhibition. Iron nanorods showed strong inhibition towards bacterial strain compared to conventional anti-bacterial drugs.	^[22]
Seed	Oil	Suppositories	Pour molding method (Macrogol, dika fat, liquid paraffin, Polyethylene glycol 1000 & 4000, petroleum ether)	Hemorrhoids	Suppositories containing Moringa seed oil showed effective results against hemorrhoids. The incorporation of seed oil in suppositories reduced their melting point.	^[23]
Leaves	Ethanolic	Oral suspension	Stirring method (Sodium carboxymethyl cellulose, propylene glycol, benzoate, sorbitol)	Hepato-protection against Isoniazid	Viscosity increases as the concentration of suspending material increases.	^[24]
Leaves	Ethanolic	Granules	Wet granulation method (Gum Arabic, HPMC, Methocel K100M CR, magnesium stearate, Avicel PH200, tween 20, 40, 80, span 20, 40, Poloxamer 407, sodium lauryl sulphate)	Anti-inflammatory and anti-arthritic	Tween 20 improved dissolution as compared to extract. Granule formation increases the solubility of M. oleifera extract, thereby effectively reducing paw thickness. Body weight reduced at first six days and later increased significantly due to gum arabica.	^[25]
Leaves	Powder	Chewable gummy tablets (CGT)	Heating and Congealing (Gelatin, high methoxyl pectin, mannitol, sucrose, propylene glycol, citric acid, corn oil, sodium benzoate)	Evaluation of Chewable gummy tablets	Pectin produced CGT with a higher swelling ratio compared to gelatin. Higher pectin and gelatin concentrations strengthened the gel structure, and the dissolution time increased CGT. Pectin-based CGT’s did not show syneresis, whereas CGT’s with 5% gelatin experienced syneresis. Higher hardness values are due to increased gelatin concentration. Pectin-based CGT had higher gumminess.	^[26]
Seeds	n-hexane	Herbal hydrogel	Mixing method (Carbopol, propylparaben sodium, methylparaben sodium, propylene glycol, triethanolamine)	Wound healing	M. oleifera hydrogel showed significant wound-healing activity. Hydrogel positively affects the proliferation of cells, granular tissue formation, and epithelization.	^[27]
Leaves	Aqueous	Phytosome	Thin-layer hydration method (soy phosphatidylcholine, TrizolTM)	Breast cancer	A dose less than 2000 mg/kg showed better in vivo assessment. Inhibition of 4T1 cells is dose-dependent.	^[28]
Leaves	Ethanolic	Emulgel	Dissolving method (Carbopol 940, triethanolamine Tween 80)	Anti-oxidant activity	After eight weeks of storage, decreased in the pH of preparation as Moringa leaves experience decomposition of fatty acid.

4. Miscellaneous Uses

A study was performed on M. oleifera using the HPLC-based cyclo condensation method. Astragalin and isothiocyanates were used as markers for standardization of the plant. The conclusive result of the study suggests that the standardized method might be useful for assessing the quality of the development of cosmetic and natural health products ^[29].

The extract of M. oleifera leaves was helpful in eliminating the adverse effects of neem oil, which is used in aquaculture as an insecticide to control predators and parasites of fish fry. The researchers concluded that the extract of M. oleifera leaves eliminated the oxidative stress and toxicity caused by neem oil ^[30].

The lower yield of okra (Abelmoschus esculentus) was studied. The low production of these crops was due to infestation by pests and insects and poor soil nutrient content. In order to improve production conditions, different chemical pesticides were used, which brought further environmental risks. The use of M. oleifera aqueous leaf extract at different concentrations (1:30 and 1:40) proved beneficial for okra ^[31].

The efficacy of M. oleifera leaf and root extract was evaluated as a plant growth regulator and biopesticide in the wheat harvest. The researcher used different concentrations (5, 10, 12.5, 25% w/w, w/v, v/v) of Moringa leaf and root extract at different stages of the wheat plant. Significant plant growth was observed, resulting in increased yield and a decrease in aphid invasion ^[32].

M. oleifera is rich in macronutrients and micronutrients, vitamins, phytohormones, alkaloids, and flavonoids, which make this plant a multipurpose plant. Recent research has shown that Moringa extract is also helpful in tolerance to abiotic and biotic stress under stressful environmental conditions ^[33].

The therapeutic effect of bioactive constituents (flavonoids, alkaloids, tannins, isothyocyanin and beta-sitosterol) present in M. oleifera has been reported in chronic diseases such as hyperlipidemia ^[34], hypertension ^[35], hepatoprotective ^[36], anti-cancer ^[37], Alzheimer’s disease ^[38], Parkinson’s disease ^[39].

The combined effect of M. oleifera and praziquantel in rats was studied by a group of researchers. The seeds and leaves of M. oleifera were considered to evaluate their bioavailability with praziquantel and also the in vivo effects of the same were observed on Taenia crassiceps. The study showed that the combined action of both had a significant amount of cytocidal activity compared to the rats, which were only administered with praziquantel ^[40].

A variety of bioactive nutrients, such as flavonoids and vitamins, is available in the M. oleifera plant. The in vitro study conducted by a group of researchers focused on bioactive compounds that make up the nutritional potential of plants ^[41]. The conclusive statement of the researcher revealed that the high content of proteins, lipids, and sulfur-containing amino acids and the relative lack of toxic components make moringa a great nutritional alternative for humans ^[42].

The bioactive isolate palmitic acid from the leaf extract of Moringa has been attributed to broad therapeutic benefits. A team of researchers studied this isolate against a wide range of microbial and fungal strains. The results showed that it had the highest zone of inhibition for both fungal and microbial strains ^[43].

The polyphenols and flavonoids present in M. oleifera to scavenge free radicals could be useful in developing an anticancer drug delivery system. Nanoparticle technology was used to incorporate Moringa extract as a drug carrier. Treatment of HeLa cell lines with a single dose of the plant showed that the composite film of the plant extract was efficient in killing malignant cells compared to other isolated and purified phytocomponents on the market ^[44].

The bioactive components of M. oleifera inhibit the inflammatory markers in lipopolysaccharide-induced human macrophages. The induced macrophages were treated with M. oleifera extract. Thereafter the treated cells were tested for their anti-inflammatory and cellular mechanism. The results revealed that the extract suppressed mRNA expression of IL -6, IL -1, NF-κB (P50), PTGS2, and TNF-α. At the same time, the inhibition of phosphorylation of IκB-α and nuclear factor (NF)-κB was also observed in the study. The researchers’ final statement suggests that the blocking of NF-κB and IκB-α may be the reason for the inhibition of inflammation ^[45].

Apart from its wide use in preventing and curing various human diseases, Moringa is known for a number of non-medicinal uses, chief among which is its use for poultry, especially in curing viral infections (Newcastle Disease Virus) and other parasitic and bacterial diseases that cause mortality in animals ^[46]. The plant also serves as an important growth promoter for farmers in the production of tomatoes, peanuts, corn, and wheat in their early vegetative stages ^[47]. Environmentally friendly biopesticides are produced from this plant, which is cheap and easily available and helps in curing various plant diseases ^[48]. Studies have shown that the total crop production increased by 20–35% by using M. oleifera leaf extract, which is a good sign for increasing agricultural growth at a minimal cost ^[49]. The aqueous extract of M. oleifera is a source of various minerals and growth promoters (indole acetic acid, gibberellins, cytokines). It thus can be used as an effective plant biostimulant that could be a simple alternative to the artificial fertilizers and pesticides available in the market ^[47]. The methanolic extract of the plant is found to be rich in potassium, calcium, carotenoid, phenols, and zeatin, and when three sprays of this extract are applied on the oilseed rape plant, it is observed that the pods, twigs, height, and number of seeds increase significantly compared to the untreated control group ^[50]. The ability of the plant to resist drought is due to the plant hormone “zeatin”, which is present in large quantities in the methanolic extract, so the plants exposed to such climatic conditions when sprayed with the methanolic extract of Moringa showed improved growth characteristics compared with well-watered plants ^[51]. The tree is efficient in removing water hardness and is used by African tribes as a cheap source compared to chemical softeners ^[52]. A study conducted by several groups found that treating river water in African countries with Moringa seeds reduced color and microorganisms by 90% and microorganism (Escherichia coli) levels by up to 95%. Previous reports indicated that a water sample treated with M. oleifera seeds reduced the hardness content of the water by 50–70%, which used to be 80.3 g L⁻¹ CaCO3 ^[53]. It has also been shown to be an effective solution for treating turbidity, alkalinity, and dissolved organic carbon. It is suggested that Moringa could be, to some extent, an alternative to chemical alum used to remove water turbidity ^[54]. Moringa is a good source for curing plant diseases and can be a good option for biopesticides ^[48]. Since various plant pathogens affect the plants, Pythium debaryanum-a pathogen responsible for damping-off disease-can be cured by adding leaves to the soil ^[55]. Nearly all plant part (fruits, flowers, leaves, seeds, roots) is believed to have different properties that can heal the body spiritually and psychologically ^[56].

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Subjects: Pharmacology & Pharmacy

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Ashutosh Pareek

Malvika Pant

Madan Mohan Gupta

Pushpa Kashania

Yashumati Ratan Bhardwaj

Vivek Jain

Aaushi Pareek

Anil Chuturgoon

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Update Date: 13 Feb 2023

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