A COMPREHENSIVE REVELATION ON PISONIA GRANDIS R. BR.

A COMPREHENSIVE REVELATION ON PISONIA GRANDIS R. BR.

G. Poongothai, S. Sindhu and S. K. Sripathi *

Department of Chemistry, Avinashilingam Institute for Home Science and Higher Education for Women Coimbatore, Tamil Nadu, India.

ABSTRACT: Medicinal plants are a huge treasure for mankind and a source of remedy for all illnesses as they are storehouses of bio-actives. The therapeutic efficiency of formulations and medicines depends on using standardized plant extracts, as The World Health Organization emphasized. The present documentation on the medicinal plant Pisonia grandis covers its pharmacological, phytochemical, biological standardization studies and the quantification protocols for the bioactive pinitol and bioactive allantoin earlier reported from this plant. This documentation sheet will aid as a reference for formulating Pisonia grandis-based herbal medicinal products.

Keywords: Standardization, Herbal formulation, Bioactive, Pisonia grandis, documentation

INTRODUCTION: The plant Pisonia grandis is scientifically well-documented for its medicinal potential. Folkloric data on this plant indicates that leaves dipped with Eau-de-Cologne reduced inflammation due to filarioid in leg. Sugar levels reduce on chewing two leaves of the plant. An interesting observation is that the sticky seeds of the plant trap small birds; therefore, it is commonly termed bird-catcher tree ¹. Sea-birds that shelter in this tree are sources of guano that farmers use to grow plants. It is a symbiotic host for many mycobionts and demonstrates ectomycorrhizal fungus association in autotrophic plants ². Due to this nature, the plant serves as a good source of nitrogen and is further proved by another report on symbiotic association ³. The plant is reported to possess anti-diabetic, wound healing, anti-oxidant, anti-microbial, anti-cancer, anti-inflammatory, anxiolytic, anti-pyretic, and hepato-protective potential. Two medicinally valuable molecules pinitol and allantoin have been isolated and characterized from the plant leaves ^{4, 5}. This revelation validates the anti-diabetic and wound-healing potential expressed by the leaf extracts.

FIG. 1 PISONIA GRANDIS ⁴

nitrogen and is further proved by another report on All parameters about standardization reported to date on this plant and its extracts have been documented in this review and comprise of data on pharmacognostic and phytochemical aspects, bio marker quantification and biological activity. All reports of earlier work, including figures are duly cited. Fig. 1 represents the picture of the plant Pisonia grandis.

Rationale: There is paucity in standardization data on medicinal plants and quantification of bioactive present in them. This remains an impediment to the large-scale production of herbal medicines and consequently leads to their unsung popularity in the drug market. To overthrow these hindrances, documentation of potential medicinal plants is a prerequisite.

TABLE 1: PROVIDES A FACT SHEET ON THE PLANT PISONIA GRANDIS

This review is a thorough revelation of the medicinal potential of Pisonia grandis. Standardization of plants and plant extracts involves the assessment and documentation of data on the following aspects.

Pharmacognostic and Phytochemical Analysis: Details of plant authentication, morphological characteristics, physicochemical characteristics, proximate parameters and qualitative phytochemical tests on plant material are necessary requisites for the standardization of plant and plant extracts

Fingerprinting of Extracts: Plant extracts' chromatographic and spectral fingerprint aid in selecting authentic plant material for herbal formulation.

Chemical Standardization: Quantifying phytochemical content and quantifying major bioactive markers in a plant extract is significant in enhancing the market value of herbal formulations.

Toxicity Studies: Toxicity studies on herbal extracts are mandatory for preparing safe herbal formulations. This review paper comprehensively documents all available data on Pisonia grandis for the ease of reference of herbal researchers and manufacturers. Standard methods and optimized protocols adopted in acquiring data on this plant are also mentioned in this document and are duly cited.

Plant Authentication: Authentication of Pisonia grandis was done at the Institute of Forest Genetics and Tree Breeding IFGTB, Coimbatore. Voucher specimens have been deposited in the herbarium of the Institute for further reference [F.No. 14932].

Extraction of Plant Material: The powdered plant material was sequentially extracted. The total ethanol extract was prepared by refluxing the plant material with ethanol for 6 hours. The sample codes of Pisonia grandis are presented in Table 2A and 2 B.

TABLE 2A: DESIGNATION OF EXTRACTS OF PISONIA GRANDIS

TABLE 2B: DESIGNATION OF PLANT MATERIAL OF PISONIA GRANDIS

Physicochemical Analysis: The data regarding the various physicochemical parameters from our earlier paper ¹⁴ is reproduced here in Tables 3 to 7 for the sake of complete documentation in this data sheet on Pisonia grandis.

TABLE 3: ORGANOLEPTIC CHARACTERISTICS OF POWDERED LEAVES, STEM AND ROOTS OF PISONIA GRANDIS

*Data reproduced from our earlier paper ¹⁴.

TABLE 4: PROXIMATE ANALYSES

*Data reproduced from our earlier paper ¹⁴

TABLE 5: EXTRACTIVE VALUES

*Data reproduced from our earlier paper ¹⁴

The gross calorific value for leaves, stems and roots of Pisonia grandis is 3848.00, 3648.00 and 4026.00 respectively. The high volatile matter content indicates that the plant is host to essential oils and fatty material, which may contribute to its wound healing potential.

TABLE 6: ELEMENTAL CONTENT OF PISONIA GRANDIS (ICP-AES METHOD)

*Data reproduced from our earlier paper ¹⁴

TABLE 7: TOXIC METAL CONTENT OF PISONIA GRANDIS (ICP-AES METHOD)

*Data reproduced from our earlier paper ¹⁴

EDX Analysis: Elemental composition of the extract of leaves, stems, and roots of Pisonia grandis was done by energy Dispersive X-ray analysis (EDX) analysis. The respective EDX spectra are represented in Fig. 2, 3 and 4. The EDX analysis ascertains the absence of heavy metals and toxic elements in the extracts.

FIG. 2: EDX SPECTRUM OF PGLE

FIG. 3: EDX SPECTRUM OF PGSE

FIG. 4: EDX SPECTRUM OF PGRE

Fluorescence Analysis ¹⁴: The fluorescence displayed by dry powdered leaves, stems and roots of Pisonia grandis when treated with chemical reagents Fig. 5 shows the presence of secondary metabolites in the plant.

FIG. 5: FLUORESCENCE ANALYSIS

Chemical Standardization of Extracts:

Qualitative Analysis: Qualitative color test results are presented in Table 8.

TABLE 8: QUALITATIVE PHYTOCHEMICAL TESTS

Spectral Finger Printing of Extracts of Pisonia Grandis: Spectral fingerprinting of medicinal plant extracts serves as a valuable authentication tool and is a recent trend adopted in plant standardization.

UV-Visible Spectral Fingerprinting: UV-Visible fingerprints of the ethanol extract of leaf, stem, and roots of Pisonia grandis were recorded in a double beam UV spectrophotometer (Shimadzu, 1601) as represented in Fig. 6.

All the fingerprints indicate the presence of polar secondary metabolites in the extracts.

FIG. 6: OVERLAY OF UV VISIBLE FINGERPRINTS OF PGLE, PGSE AND PGRE

FT-IR Spectral Fingerprinting: The FT-IR spectral fingerprints were recorded in FTIR spectrometer Shimadzu, IR Affinity 1. The fingerprints Fig. 7, 8 and 9 may be considered specific for the respective parts of this plant. While the IR spectrum of the leaf extract indicates a moderate absorption, the stem and root extracts reveal intense absorptions due to glycosides. All three fingerprints indicate comparably similar absorptions in the range 3400 to 2800 cm^-1.

FIG. 7: IR FINGERPRINT OF PGLE

FIG. 8: IR FINGERPRINT OF PGSE

FIG. 9: IR FINGERPRINT OF PGRE

NMR Spectral Fingerprinting: ¹H NMR spectral fingerprints of pet-ether and ethanol extracts of leaves, stems and roots of Pisonia grandis were recorded in Bruker Avance III 500 MHz spectrometer with DMSO/CDCl₃ solvent as the case may be. The ¹H NMR spectral fingerprints of the pet-ether, ethanol and water extract of leaves, stems and roots, of Pisonia grandis are represented in Fig. 10 to 15. The ¹H NMR spectral fingerprints of the polar ethanol extracts indicate peaks characteristic of the biomarker allantoin (expected  at 5.24 ppm as doublet, 5.83ppm as singlet, 6.96 ppm as doublet, 8.06ppm  as singlet ^{4, 5} and of biomarker pinitol in the range 3.0-4.0 ppm ^{4, 5}.

FIG. 10: ¹H NMR FINGERPRINT OF PGLP                   

FIG. 11: ¹H NMR FINGERPRINT OF PGLE

FIG. 12: ¹H NMR FINGERPRINT OF PGSP                  

FIG. 13: ¹H NMR FINGERPRINT OF PGSE

FIG. 14: ¹H NMR FINGERPRINT OF PGRP                           

FIG. 15: ¹H NMR FINGERPRINT PGRE

¹³CNMR Finger Printing: ¹³ C NMR spectral finger prints of the pet-ether and ethanol extract of leaves, stems and roots of Pisonia grandis were recorded in Bruker Avance III 500 MHz spectrometer. The respective ¹³C NMR spectral finger prints are represented by Fig. 16 to 21.

FIG. 16: ¹³ C NMR FINGERPRINT OF PGLP                    

FIG. 17: ¹³ C NMR FINGERPRINT OF PGLE

FIG. 18: ¹³ C NMR FINGERPRINT OF PGSP                  

FIG. 19: ¹³ C NMR FINGERPRINT OF PGSE

FIG. 20: ¹³ C NMR FINGERPRINT OF PGRP                 

FIG. 21: ¹³ C NMR FINGERPRINT OF PGRE

The ¹³ C NMR spectral fingerprints of the polar ethanol extract of leaves clearly indicate peaks characteristic of the biomarkers allantoin (at 63.5 and 158.9 ppm) and pinitol (at 60.0 ppm due to the lone methoxyl carbon and at 84.3 ppm due to the ipso carbon to which the methoxyl group is attached in pinitol ^{4, 5}. The stem and root ethanol extracts additionally indicate the presence of glycosides.

Chromatographic Finger Printing:

Thin Layer Chromatographic Analysis: The optimized solvent systems for TLC analysis of pet-ether, dew axed ethanol, aqueous extracts of Pisonia grandis are listed in Table 9. Thin layer chromatograms for the standard and isolated bioactive are represented in Fig. 22 and 23. The relative factor of pinitol is 0.5 and that of allantoin is 0.62 in the respective developing solvents indicated below.

TABLE 9: OPTIMIZED SOLVENT SYSTEMS FOR TLC

FIG. 22: TLC CHROMATOGRAM OF ISOLATED ISOLATED ALLANTOIN WITH STANDARD      

FIG. 23: TLC CHROMATOGRAM OF PINITOL WITH STANDARD

HPTLC Fingerprinting: HPTLC analysis was performed in Camag HPTLC system (Camag Linomat V semi automatic spotting device and WinCATS 4 software version 4.05).

The protocols adopted for HPTLC analysis are given below. HPTLC densitograms of the ethanol extracts of leaves, stems and roots of Pisonia grandis and the respective dewaxed extracts are represented in Fig. 24 to 29.

FIG. 24: HPTLC DENSITOGRAM OF PGLE                    

FIG. 25: HPTLC DENSITOGRAM OF PGSE

FIG. 26: HPTLC DENSITOGRAM OF PGRE                      

FIG. 27: HPTLC DENSITOGRAM OF DPGLE

FIG. 28: HPTLC DENSITOGRAM OF DPGSE                     

FIG. 29: HPTLC DENSITOGRAM OF DPGRE

High-Performance Liquid Chromatographic Fingerprinting: High-Performance Liquid Chromatographic (HPLC) analysis was done to assess the phytochemical profile of the plant Pisonis grandis (Schimadzu Class VP V6.14SP2 HPLC instrument). Overlay of HPLC Chromato-grams of ethanol extracts of Pisonia grandis (PGLE, PGSE and PGRE) with standard markers pinitol and allantoin are presented in Fig. 30 and 31. The HPLC protocols adopted are presented below:

FIG. 30: OVERLAY OF HPLC CHROMATO-GRAMS OF PGLE, PGSE AND PGRE AND STANDARD MARKER PINITOL

FIG. 31: OVERLAY OF HPLC CHROMATOGRAMS OF PGLE, PGSE AND PGRE ANDSTANDARD MARKER ALLANTOIN

GC-MS Fingerprinting: GC-MS fingerprints of the extracts were recorded in Hewlett–Packard 6890 gas chromatograph (Agilent Technologies, CA) coupled to an HP5973 mass selective detector. The protocol adopted is given below.

GC MS Protocol:

Column used: Agilent Ultra 2 fused silica capillary column (12 m length, 0.2 mm internal diameter).

Carrier Gas: Helium.

Flow Rate: 1 ml/min.

Sample Injection: Splitless mode.

Initial Temperature: 100°C.

Final Temperature: 400 °C.

Concentration of the Sample: 1 ppm.

Run Time: 36 min.

The total ion chromatograms Fig. 32 to 37 indicate that the non-polar extracts possess major constituents with retention time ranging from 22 to 26 minutes. The polar extracts express a broad peak in common and other major peaks beyond 30 minutes retention time. As predicted by the NIST database, the major phyto-constituents in the non-polar extracts have been reported as n-hexadecanoic acid (palmitic acid), 6-octadecenoic acid, 9-octadecenoic acid and 9-octadecenoic acid 1,2,3-propanetriyl ester ⁴⁵.

FIG. 32: GC FINGERPRINT OF PGLP                   

FIG. 33: GC FINGERPRINT OF PGLE

FIG. 34: GC FINGERPRINT OF PGSP

FIG. 35: GC FINGERPRINT OF PGSE

FIG. 36: GC FINGERPRINT OF PGRP     

FIG. 37: GC FINGERPRINT OF PGRE

Quantitative Analysis:

Quantification of Phytochemicals: The phenolic and flavonoid content of the leaves and stem bark was estimated by Folin-Ciocalteu and aluminium chloride colorimetric assay, respectively. The phytochemical content reported for crude extracts of Pisonia grandis is presented in Table 10.

TABLE 10: QUANTIFICATION OF PHYTOCHEMICALS

 *For leaf extract phenolic, flavonoid and tannin contents are expressed as catechol, quercetin, and catechin equivalents per gram extract. Stem bark extracts are expressed as gallic acid and quercetin equivalents for phenolic and flavonoid contents, respectively as Mean±S.D (n=3).

Quantification of Nutritive Content: The fiber, protein and soluble carbohydrate (g/100g) content of leaves was determined by acid-base digestion, Kjeldahl method and difference method respectively ¹⁶. The leaves are a source of fiber also.

TABLE 11: NUTRITIVE CONTENT OF PISONIA GRANDIS ¹⁶

Quantification of Biomarkers: The biomarkers allantoin and pinitol present in the leaves of this plant were quantified by HPLC (Shimadzu Class VP V6.14SP2) ⁴⁶. The protocols adopted are presented below, and the quantification details are tabulated in Table 12. The respective chromatograms are represented in Fig. 38 and 39. These biomarkers were first reported from leaves of this plant ^{4, 5}.

HPLC Protocol for Allantoin:

Column: C18 column

Mobile Phase: acetonitrile: phosphate buffer (20:80)

Detector: Photo Diode Array detector (PDA)

Standard: Allantoin Sigma brand

Concentration of Standard: 10mg in 1ml of water

Injected Volume: 20µl

HPLC Protocol for Pinitol:

Column: Amine column

Mobile Phase: acetonitrile: water (70:30)

Detector: Refractive Index detector (RI)

Standard: Pinitol Sigma brand

Concentration of Standard: 10mg in 1ml of water

Injected Volume: 20µl

FIG. 38: HPLC OF ALLANTOIN                                         

FIG. 39: HPLC OF PINITOL

TABLE 12: QUANTIFICATION OF BIOMARKERS

Biological Standardization: The plant is known for its anti-diabetic, anti-arthritic and wound healing potential and there are numerous reports on the medicinal potential of leaves in particular. The bioactive molecules allantoin and pinitol have been isolated and reported from this plant and since then there is a surge of scientific reports on the medicinal potential of Pisonia grandis. Available reports on the biological potential of the plant have been reviewed in this section and the results of the studies compared and presented in Tables 13-15. The references are duly cited.

Antidiabetic Activity: The first report on in-vivo anti-diabetic effect of the ethanol extract of the plant, revealed the α-glucosidase inhibitory activity in a dose dependant manner and the IC₅₀ value was 416.7 µg/ml ¹³. The other reports are in-vitro studies on the anti-diabetic efficacy of the leaf ethanol extract revealing high inhibition of α-amylase ¹⁷. The stem bark hexane extract of the plant was also found to exhibit potent α-amylase inhibitory activity ¹⁵.

Antioxidant Activity: The first report of antioxidant activity of the plant was reported by Subhasree et al. in 2009. The methanol extract of leaves was evaluated for its capacity to scavenge free radicals by in-vitro method at concentrations ranging from 50 to 250µg/ml. The IC₅₀ values of the methanol extract in DPPH radical scavenging assay, ABTS radical cation-scavenging assay, and inhibition of lipid peroxidation assay was 175µg/ml, 80µg/ml and 505µg/ml, respectively. This study highlights the plant's tremendous nutritional potential and its importance in the prevention of diseases caused by free radicals ¹⁸. A similar report of the antioxidant activity of the leaf methanol extract (maceration with methanol for 15 minutes) was reported by Jagadeesan et al.,¹⁹. The crude ethyl acetate extract of stem bark exhibits strong antioxidant activity with IC₅₀ value of 148.2µg/ml ¹⁵. A biherbal extract containing Pisonia grandis and Cardiospermum helicacabum also showed high antioxidant activity ²⁰. Antiquorum sensing effect of the methanol extract of leaves was also assessed and the extract shows 88.25±0.82 % biofilm inhibition against Pseudomonas aeruginosa ²¹. The electrochemical response of the extracts of Pisonia grandis by cyclic voltammetry was reported by Shubashini et al., ²². Table 13 gives the results of antioxidant assays on various parts of Pisonia grandis carried out in our laboratory ⁴⁵. Table 14 provides data on antioxidant activity for the free radical-scavenging assays reported earlier.

TABLE 13: IN-VITRO ANTIOXIDANT ACTIVITY (BY DPPH RADICAL SCAVENGING)

TABLE 14: FREE RADICAL-SCAVENGING ASSAY

Antimicrobial Activity: There are five reports till date on antimicrobial potential of the leaves of this plant and one report on antimicrobial potential of the stembark of the plant. The antimicrobial potential of the extracts of Pisonia grandis as reported till date is documented in Table 15.

TABLE 15: ANTIMICROBIAL ACTIVITY OF SOLVENT EXTRACTS OF PISONIA GRANDIS

Anti-Inflammatory Activity: Leaves have been well investigated for their acute and chronic anti-inflammatory potential. Anti-inflammatory activity was first reported in 2002 for the chloroform extract of leaves of the plant. The study revealed that the chloroform extract exhibited chronic anti-inflammatory activity at a dosage of 500mg/kg, equivalent to diclofenac at 50mg/kg ²⁸. A similar report wherein the leaf ethanol and aqueous extracts of Pisonia grandis (cold maceration for 3-7 days) was tested against carrageenan-induced paw edema indicated that both extracts exhibited substantial anti-inflammatory effects against infusion of carrageenan injection ⁸. The methanolic extract and flavonoid rich ethyl acetate extract of leaves of Pisonia grandis were found to significantly decrease acute and chronic phase inflammation ²³. Compared to aqueous and alcoholic extracts of roots of the plant, the alcoholic extract reduced paw edema significantly ²⁹. A topical formulation prepared with chloroform extract of leaves showed a considerable reduction in carrageenan induced paw edema ³⁰.

Anti-Arthritic Activity: Anti-arthritic activity of the plant was first reported in leaves by Elumalai et al., in 2012. The ethanol extract of leaves [Soxhlet extraction] was assessed by Freund’s adjuvant induced arthritis model ³¹. In-vitro assessment of anti-arthritic potential of pet-ether and ethanol extract of leaves, stems and root was carried out by Poongothai et al. ³² The study revealed that the pet-ether and ethanol extracts of leaves exhibited significant anti-arthiritic potential equivalent to that of palmitic acid at the same concentration. In yet another assay of a biherbal extract composed of ethanolic extract of Pisonia grandis and cardiospermum helicacabum, indicated a greater inhibition of protein denaturation compared to the individual extracts ³³.

Wound Healing Potential: The leaf methanol extract (1% and 2% w/w concentration) in an ointment formulation, demonstrated considerable wound healing activity in incision and excision wound models ³⁴. The potential of the plant to cure injuries has also been validated by chick chorioallantoic membrane (CAM) in-vitro assay by Poongothai et. al in 2019.

In addition to significant anti-diabetic, anti-microbial, anti-oxidant, anti-inflammatory, anti-arthritic and wound healing potential, the plant has also been tested for its effectiveness as an analgesic ²⁸, diuretic ²⁸, anxiolytic ³⁵, anti-ulcer ³⁶ and hepatoprotective ^{29, 37} agent. A polyherbal formulation consisting of leaves of Pisonia grandis is reported with anti-pyretic activity comparable with the standard drug paracetamol at the dose levels of 150mg/kg and 300mg/kg ⁹. The hepatoprotective and anti-inflammatory action of roots was reported by Majumdar et al., in 2012 ²⁹. An in-vitro anti-quorum sensing effect of the methanol extract of the leaves of the plant with 88.25 ± 0.82% inhibition has been reported recently ²¹. This report opens up avenues for the discovery of anti-quorum sensing agents from Pisonia grandis. The findings may be significant in the light of increased multi-drug resistance by pathogenic bacteria.

In summary, with regard to the medicinal potential of Pisonia grandis, significant research has been done on the leaves, whereas roots and stem bark are found to be less investigated. Revelation on the presence of two potentially medicinal molecules allantoin and pinitol in the extracts of this plant provides the intellectual input to formulating wound healing ointments and anti-diabetic formulations. Both molecules have been thoroughly validated scientifically.

Toxicity Studies: Acute oral toxicity studies have been reported on leaf ethanol extract of Pisonia grandis. As reported ^{8, 12, 35, 36}, no toxic symptoms were observed up to a dosage of 2000mg/kg body weight. Pisonia grandis leaf ethanol extract is considered safe for oral administration. This fact was reaffirmed by the toxicity study of a polyherbal formulation ⁹ of which Pisonia grandis constituted one-fifth of the concentration of the formulation that showed no mortality even at the dosage of 1000mg/kg body weight. Yet another biherbal formulation ³³ containing Pisonia grandis ethanolic extract as one of its constituents revealed no toxic symptoms upto 2000mg/kg body weight. Still, a higher dose level of 5000mg/kg body weight brought adverse symptoms like dyspnea. Hence the recommended therapeutic dose level of leaf extract of Pisonia grandis is 2000mg/kg body weight. All studies on toxicity assessment are reported to have been carried out according to OECD 423 guidelines.

Pisonia Grandis Mediated Nanoparticle Synthesis: Silver nanoparticles (AgNPs) synthesized from Pisonia grandis ³⁸ exhibited significant antifungal activity ³⁹ and found to be useful in biomedical imaging ⁴⁰. The zinc oxide (ZnO) and magnesium oxide (MgO) nanoparticles from leaf extract of Pisonia grandis were found to exhibit high anti-bacterial activity against M. luteus and K. pneumonia and a higher anti-fungal activity against C. albicans strain. Thus, Pisonia grandis may find prospective applications in the biomedical field also.

Medicinal Products Formulated with Leaf Extract of Pisonia Grandis: Herbal food supplements in the form of tablets comprising of the Pisonia grandis leaf extract have been formulated to treat diabetes mellitus ⁴¹. The allantoin-rich leaf extract of the plant was incorporated in skin whitening, moisturizing creams, and sunscreen lotions ^{42, 43}. Fabric coated with leaf extracts of Pisonia grandis has been validated as an anti-microbial herbal bandaging ⁴⁴. A topical wound healing ointment with extracts of Pisonia grandis formulated in our laboratory has received a patent grant ⁴⁸.

CONCLUSION: All available reports up to date on the plant Pisonia grandis are documented herein as a ready record, which will aid herbalists in preparing standardized formulations of the plant that will fetch global market value. Literature reports on the medicinal plant Pisonia grandis since the last two decades are a scientific validation of its medicinal potential, in particular its leaf extracts. Safe and efficacious medicinal preparations such as skin creams and wound healing ointments based on allantoin and pinitol containing leaf extracts of Pisonia grandis will be prospective for communities that largely rely on folkloric and traditional medicines. This comprehensive revelation of the medicinal potential of Pisonia grandis provides substantial ground for formulating safe and efficacious herbal products by the local people from fresh leaves of Pisonia grandis from their garden. Since the leaves are host to anti-diabetic, insulin-mimetic pinitol and wound-healing allantoin, the leaf extract may be potentially effective in curing diabetic foot ulcers. The validation of this efficacy will be taken up in our laboratory.

ACKNOWLEDGEMENT: The authors thank Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, for providing facilities to carry out this work. The authors also duly acknowledge the contributing authors of research papers cited in this work for providing scientific data on the plant.

CONFLICTS OF INTEREST: The authors declare no conflict of interest.

REFERENCES:

1. Tamizhazhagan V and Pugazhendy K: Ethno botanical and Phyto pharmacological review of Pisonia alba Asian Journal of Pharmacology and Clinical Research 2017; 10(5): 69-71.
2. Hayward JA and Horton TR: Edaphic factors do not govern the ectomycorrhizal specificity of Pisonia grandis (Nyctaginaceae). Mycorrhiza 2012; 22(8): 647-52.
3. Sharples JM and Cairney JW: Assimilation of inorganic nitrogen by a mycobiont isolated from Pisonia grandis Br. (Nyctaginaceae). Mycorrhiza 1998; 7(5): 255-60.
4. Sripathi SK, Poongothai G and Lalitha P: Antidiabetic agent Pinitol from the leaves of Pisonia grandis (R. Br.). Journal of Natural Remedies 2011; 11(1): 39-43.
5. Sripathi SK, Gopal P and Lalitha P: Allantoin from the leaves of Pisonia grandis Br. Int. Journal of Pharmaceutical and Life Sciences 2011; 2(6): 815-17.
6. Ilango K: β-sitosterol glucoside from Pisonia grandis Br. Stem bark in ethyl acetate extract. International Journal of Green Pharmacy 2018; 12(1): 66-8.
7. Natarajan RK, Ragothaman P, Veluchamy G and Balakrishna K: Chemical examination of Pisonia grandis. Bulletin Medico-Ethno Botanical Research 1990; 1: 1-0.
8. Sutthivaiyakit S, Seeka C, Wetprasit N and Sutthivaiyakit P: C-methylated flavonoids from Pisonia grandis Phytochemistry Letters 2013; 6(3): 407-11.
9. Radha R, Arokiyaraj S, Agastian P, Balaraju K, Kumar RM and Bula P: Phytochemical analysis and anti inflammatory activity of Pisonia grandis Br. Biomedical & Pharmacology Journal 2008; 1(1): 127-30.
10. Elumalai A, Eswaraiah MC, Sindhura S, Rajendra D, Manikanta KV and Rajkumar CH: Acute toxicity studies and antipyretic activity of a Polyherbal formulation. International Journal of Biological & Pharmaceutical Research 2012; 3(1): 130-32.
11. Padmini N, Sundaramoorthy SD, Tripathi H and Hari R: In vitro and in vivo antiarthritic activity of combined ethanolic extracts of Pisonia grandis and Cardiospermum halicacabum in Wistar rats. Journal of Applied Pharmaceutical Sciences 2016; 6(9): 102-8.
12. Rahman H, Elumalai A, Eswaraiah MC and Bardalai D: Evaluation of anxiolytic activity of ethanolic extract of Pisonia grandis R. Br leaves in mice. Journal of Chemical and Pharmaceutical Research 2011; 3(5): 646-52.
13. Kalichelvan Kaliyamoorthy PA: α-Glucosidase inhibitory and antidiabetic activities of ethanolic extract of Pisonia alba Span leaves. International Journal of Integrative Biology 2009; 6(1): 41-45.
14. Poongothai G and Sripathi SK: Documentation of physicochemical parameters of the folkloric medicinal plant Pisonia grandis Br. reared under greenhouse and local environment conditions. Research Journal of Medicinal Plant2015; 9(8): 427-34.
15. Mohan V, Ramasamy M, Vemuri S and Kaliappan I: A study on phytochemical screening, antioxidant, antimicrobial and α-αmylase inhibitory activities of crude extracts of the stem bark of Pisonia grandis, r. Br. Asian Journal of Pharmacology and Clinical Research 2017; 10(11): 129-32.
16. Arasaretnam S, Kiruthika A and Mahendran T: Nutritional and mineral composition of selected green leafy vegetables. Ceylon Journal of Science 2018; 47(1): 35-41.
17. Lalitha P and Sripathi SK: in-vitro anti diabetic efficacy (potential) of leaf ethanol extract fractionates of Pisonia grandisBr. Pharmacophore 2016; 7(6): 625-30.
18. Subhasree B, Baskar R, Keerthana RL, Susan RL and Rajasekaran P: Evaluation of antioxidant potential in selected green leafy vegetables. Food Chemistry 2009; 115(4): 1213-20.
19. Jagadeesan P, Prasad DA, Pandikumar P and Ignacimuthu S: Antioxidant and free radical scavenging activities of common wild greens from Tiruvallur District of Tamil Nadu, India. Indian Journal of Natural Products and Resources 2011; 2(2): 156-163.
20. Shobana Devi S, Nandhini P, Himanshu T and Rajeswary H: Antioxidant Activity of Combined Ethanolic Extract of Pisonia grandis and Cardiospermum halicacabum. International Journal of Pharmaceutical Sciences Review and Research 2016; 39(1): 95-100.
21. Chattopadhyay A, Dixit B, Nijhawan P, Kamarudheen N and Rao B: Phytochemical screening, in vitro anti-quorum sensing activity and antioxidant activity of extracts of Plumeria alba, Pisonia alba and Cynodon dactylon. Journal of Applied Pharmaceutical Sciences 2017; 7 (02): 162-166.
22. Sripathi SK, Subashree M and Lalitha P: Cyclic voltammetric behaviour of the ethanol extracts of Pisonia grandis (R. Br). Asian Journal of Biochemical and Pharmaceutical Research 2011; 1(3): 30-47.
23. Jayakumari S, Arthanareswaran A, Vijayalakshmi A, Velraj M and Ravichandran V: Free radical scavenging activity of Pisonia grandis Br leaves. International Journal of Pharmaceutical Education and Research 2012; 46(1): 34-37.
24. Murugesh S and Vino P: Phytochemical constituents, antioxidant activity and FT-IR analysis of Pisonia grandis leaf extracts. International Journal of Pharmacognosy and Phytochemical Research 2017; 9(7): 933-938.
25. Sripathi SK and Poongothai G: Bioassay-guided fractionation and anti-fungal activity studies on Pisonia grandis Br. Wounds. International Journal of Pharmacognosy and Phytochemical Research 2013; 5(1): 1-3.
26. Jayakumari S, Ravichandiran V and Rao N: Antimicrobial activity of Pisonia grandis Br leaf extract and its fraction.World Journal of Pharmacy and Pharmaceutical Sciences 2014; 3(2): 2290-302.
27. Pradheesh G, Suresh J, Suresh S and Alexramani V: Antimicrobial activity and identification of potential ethanolic antimicrobial compounds from the medicinal plant Pisonia grandis Br. World Journal of Pharmaceutical Sciences 2017; 6(4): 1686-700.
28. Anbalagan N, Rajinikanth KN, Gnanasam SK, Leonard JT, Balakrishna K, Ramachandran S and Sridhar SK: Analgesic, anti-inflammatory and Diuretic Activities of Pisonia grandis. Natural Product Sciences 2002; 8(3): 97-9.
29. Majumdar A, Sahu M, Saraf S, Verma S and Yadav R: Evaluation of Hepatoprotective and Anti-inflammatory Activity of Roots of Pisonia grandis Br. Inventi Impact 2012; Plant Activa (3): 158-62.
30. Kumar PR, Vijayalakshmi A, Priyadarshini S and Mounika A: Development and evaluation of topical formulation with chloroform extract of Pisonia grandis leaves for anti inflammatory effect A. International Journal of Chem Tech Research 2014; 6(5): 2660-667.
31. Elumalai A and Prakash YG:Evaluation of anti arthritic activity of ethanolic extract of Pisonia grandis Br. Asian Journal of Pharmaceutical Research 2012; 2(3): 91-93.
32. Poongothai G and Sripathi SK: Inhibition of protein denaturation by extracts of leaves, stems and roots of Pisonia grandisBr. International Research Journal of Pharmacy 2018; 9(5): 53-56.
33. Padmini N, Sundaramoorthy SD, Tripathi H and Hari R: In vitro and in vivo antiarthritic activity of combined ethanolic extracts of Pisonia grandis and Cardiospermum halicacabum in Wistar rats. Journal of Applied Pharmaceutical Sciences 2016; 6(9): 102-8.
34. Prabu D, Nappinnai M, Ponnudurai K and Prabhu K: Evaluation of wound-healing potential of Pisonia grandis Br A preclinical study in Wistar rats. The International Journal of Lower Extremity Wounds 2008; 7(1): 21-27.
35. Rahman H, Elumalai A, Eswaraiah MC and Bardalai D: Evaluation of anxiolytic activity of ethanolic extract of Pisonia grandis R. Br leaves in mice. Journal of Chemical and Pharmaceutical Research 2011; 3(5): 646-52.
36. Amudha P, Subathiradevi P and  Periyanayagi M: Evaluation of antiulcer activity of hydroalcoholic leaf extract of Pisonia grandisBr using indomethacin and pylorus ligation induced gastric ulcer in rats. International Journal of Universal Pharmacy and Bio Sciences 2020; 9(4): 123-136.
37. Thenmozhi S, Kameshwaran S, Subasini U, Sathyamurthy D and Dhanalakshmi M: Hepatoprotective Constituents from the Leaves of Pisonia grandis Br. Pharmacologia 2013; 4: 383-90.
38. Firdhouse MJ, Lalitha P and Sripathi SK: Novel synthesis of silver nanoparticles using leaf ethanol extract of Pisonia grandis (R. Br). Der Pharma Chemica 2012; 4(6): 2320-2326.
39. Jannathul Firdhouse M and Lalitha P: Biocidal potential of biosynthesized silver nanoparticles against fungal threats. Journal of Nanostructure in Chemistry 2015; 5(1): 25-33.
40. Devendiran RM, Chinnaiyan SK, Mohanty RK, Ramanathan G, Singaravelu S, Sobhana SS and Sivagnanam UT: Sunlight mediated biosynthesis and characterisation of gold nanoparticles using Pisonia grandis leaf extract for biomedical applications. Journal of Biomaterials and Tissue Engineering 2014; 4(6): 430-8.
41. Kumaran PS and Saranyambiga D: Formulation and evaluation of herbal food supplement containing lettuce leaves (Pisonia grandis br) extract. Shanlax International Journal of Arts, Science & Humanities 2015; 2(4): 123-30.
42. Sripathi SK and Lalitha P: Allantoin rich extracts of Pisonia alba and use thereof in cosmeceutical products .IN2012CH00084 A 2013;
43. Lalitha P, Sripathi SK and Jayanthi P: UV protecting ability of sunscreen lotions prepared with extracts of Pisonia grandis Br.World Journal of Pharmacy and Pharmaceutical Sciences 2015; 4: 324-9.
44. Amasamani S, Lalitha P and Sripathi SK: A process of preparation of herbal bandaging fabric coated with leaf extracts of Pisonia grandis and products thereof IN202141015486 A 2021;
45. Poongothai G 2014 Isolation, Characterization of Chemical Constituents and Validation of Herbal Potential of Folkloric Medicinal Plants Pisonia grandisBr. and Andrographis stenophylla C.B Clarke Doctoral dissertation, Avinashilingam Institute for Home Science and Higher Education for Women, Shodhganga.
46. Poongothai G and Sripathi SK: Quantitative analysis of allantoin leaves, stem and roots of Pisonia grandis by RP-HPLC. Inter J of Current Research 2013; 5(8): 2105-08.
47. Sarvananda L and Premarathna AD: Investigation of total phenolic, tannins, flavonoid contents, and antioxidant activity of Pisonia alba. Pharmacophore 2021; 12(6): 43-49.
48. SK Sripathi and Pottail L: Wound healing topical ointment from solvent extracts of Pisonia grandis and products thereof, Patent Number 410082, 27.10.2022, The Patent Office, GOI.
    

    ---

    How to cite this article:

    Poongothai G, Sindhu S and Sripathi SK: A comprehensive revelation on Pisonia grandis R. BR.. Int J Pharm Sci & Res 2023; 14(6): 2738-54. doi: 10.13040/IJPSR.0975-8232.14(6).2738-54.

    ---

    All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.