{"id":58862,"date":"2024-06-25T10:48:25","date_gmt":"2024-06-25T10:48:25","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=58862"},"modified":"2024-07-03T17:34:56","modified_gmt":"2024-07-03T17:34:56","slug":"anti-inflammatory-antioxidant-and-wound-healing-properties-of-the-methanolic-extracts-from-hedera-helix-fruits-and-leaves","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/anti-inflammatory-antioxidant-and-wound-healing-properties-of-the-methanolic-extracts-from-hedera-helix-fruits-and-leaves\/","title":{"rendered":"Anti-inflammatory, Antioxidant, and Wound-healing Properties of the Methanolic Extracts from Hedera helix Fruits and Leaves"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Herbal\nmedicine, often called phytotherapy or botanical therapy, has been more\nwell-liked in recent years because of its apparent therapeutic advantages and\ndecreased risk of side effects compared to synthetic medications1<\/sup>. Many people\nview natural sources as a more holistic and sustainable approach to healthcare.\nPlants contain various chemical compounds, including alkaloids, flavonoids, and\nterpenoids, which can have medicinal properties. The complexity of these\ncompounds allows for a broad spectrum of therapeutic effects2<\/sup>. In recent\nyears, there has been an increasing interest in studying the efficacy and\nsafety of herbal remedies. However, it’s essential to approach herbal medicine cautiously,\nseeking guidance from qualified practitioners and considering potential\ninteractions with other medications or health conditions. Furthermore, further\nresearch is necessary to better understand the effectiveness and safety of\ndifferent herbal remedies.<\/p>\n\n\n\n

Hedera helix<\/em>, commonly known as ivy or English ivy, is a member of the\nAraliaceae family and is native to Europe and western Asia. It is a versatile\nand vigorous evergreen climber, known for its attractive appearance. It is\noften grown as an ornamental plant for its dark green leaves and ability to\nscale walls and cover surfaces3<\/sup>.  <\/p>\n\n\n\n

People have topically applied the H. helix <\/em>as a remedy for\nremoving benign warts. The extract of H. helix <\/em>contains compounds with\nantioxidant properties that protect cells from oxidative damage caused by free\nradicals. Antioxidants are generally associated with potential health benefits4<\/sup>. Additionally,\nit may help relax smooth muscles, potentially making it useful for conditions\ninvolving muscle spasms or bronchial constriction. This effect may help manage\nconditions involving bronchial spasms, such as asthma. It can help thin and\nloosen mucus in the respiratory tract5<\/sup>. This can be\nparticularly beneficial for individuals with productive acute coughs, making it\neasier to expel mucus6<\/sup>.<\/p>\n\n\n\n

Some studies have reported positive effects on respiratory\nfunctions, including improved lung function7<\/sup>. However,\nfurther research is necessary to validate these effects and establish suitable\ndosages. It may help reduce allergic responses in some cases. Preliminary\nstudies have suggested that certain compounds found in H. helix <\/em>extract\nmay exhibit antitumor properties8<\/sup>. Some studies\nhave suggested that it may have a role in improving glucose metabolism and\ninsulin sensitivity. However, more research is necessary to determine its\neffectiveness in managing diabetes9<\/sup>.<\/p>\n\n\n\n

Researchers have long explored herbal remedies for their potential\nanti-inflammatory and anti-cancer properties. Such a diverse array of bioactive\ncompounds in H. helix <\/em>leaves suggests its potential for various\ntherapeutic applications, like phenolic acids and flavonoids10<\/sup>, known for\ntheir antioxidant properties. They can help neutralize harmful free radicals in\nthe body and reduce oxidative stress. They have anti-inflammatory effects and\ncan potentially strengthen blood vessels and reduce the risk of cardiovascular\nissues. <\/p>\n\n\n\n

The current study aimed to determine the total phenolic, flavonoid,\nand tannin content of methanolic extracts of H. helix <\/em>fruits and leaves.\nAdditionally, the extracts’ antioxidant qualities were evaluated using DPPH,\nFRAP, and ABTS tests. The study also assessed the possible anti-inflammatory\nproperties of the extracts, as well as their wound-healing qualities on adult\nalbino rats through ointments made from the extracts.<\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

Plant material <\/strong><\/p>\n\n\n\n

H. helix <\/em>leaves and ripe fruits were collected in September 2023 from the\nMutah University campus in Al-Karak, south Jordan. After that, dust and dirt\nwere eliminated from the ripe fruits and fresh leaves by washing them under\nrunning tap water without squeezing them. The ripe fruits and fresh leaves were\nair-dried in the shade for fourteen days at room temperature. An electronic\nblender was used- to grind the dried leaves and fruits, which were then put\nthrough a 40-mesh screen and kept in a closed glass container for later use.\nUsing 100 ml of 95% methanol, the powdered portion (20 g) was macerated for 24\nhours while being stirred periodically. After filtering, the methanol extract\nwas placed in a rotating evaporator for three hours to evaporate the methanol\nand concentrate the extract. <\/p>\n\n\n\n

Total Phenolic Content (TPC) <\/strong><\/p>\n\n\n\n

The total soluble phenolic component in the various ivy extracts\nwas ascertained using the Folin-Ciocalteu reagent11<\/sup>. Half a\nmilliliter of the extract was combined with 2.5 ml of Folin-Ciocalteu reagent\n(which had been diluted 10-fold with distilled water) and 2 ml of 7.5% Na2<\/sub>CO3<\/sub>\nafter the extract made from methanol had been diluted to a concentration of one\nmg\/mL. After ninety minutes of incubation at thirty degrees Celsius, the\nsamples were analyzed for absorbance at 765 nm using a spectrophotometer\n(HITACHI U-5100 UV-VIS) against a blank sample. The amount of phenolics in the\nextracts was expressed using gallic acid equivalent (mg GA\/g extract). Each\nvalue was consistently stated as one gram of the relevant dry weight of the\nplant extract. All measurements were repeated three times<\/p>\n\n\n\n

 Determination of total\nflavonoid content:<\/strong><\/p>\n\n\n\n

The total amount of flavonoid in 95% methanol plant extracts was\nquantified using the AlCl3 <\/sub>technique12<\/sup>. Briefly, a 2%\nAlCl3<\/sub>.6H2<\/sub>O solution was mixed with 20 \u00b5L of the extract.\nThe mixture was shaken vigorously, and 10 ml of water that had been\ndouble-distilled was added to dilute it. After 10 minutes of incubation, the\nabsorbance for the reaction mixture was measured using an ultraviolet-visible\nspectrophotometer (HITACHI U-5100 UV-VIS) at 440 nm. The flavonoid content was\nquantified- in milligrams per gram of dry material, or Trolox equivalents.\nThree duplicates of each determination were made.<\/p>\n\n\n\n

Estimation of Total Tannin Content <\/strong><\/p>\n\n\n\n

The Folin-Ciocalteu method was applied to ascertain the total tannin\ncontent13<\/sup>. About 0.1 mL\nof the extract was added. Then a volumetric flask (10 mL) was filled with 7.5\nmL of distilled water.  Half a milliliter\nof Folin-Ciocalteu phenol reagent, one milliliter of 35% sodium carbonate\nsolution, and diluted to 10 mL after distilled water was added.\nThe mixture was left at ambient temperatures for half an hour. Using the same\nprocedure, a series of reference standard solutions of gallic acid were made.\nUsing a spectrophotometer, the absorbance of the test and standard solutions at\n700 nm against the blank was measured. Three separate measurements of the\ntannin content were made. <\/p>\n\n\n\n

DPPH free radicals scavenging activity<\/strong><\/p>\n\n\n\n

The standard approach14<\/sup> was applied with appropriate modifications to assess the plant extract’s ability to scavenge DPPH free radicals15<\/sup>. A solution of DPPH (10 mg) in 250 mL of methanol was created, yielding a 40 \u00b5g\/ml concentration. A concentration of 1 mg\/mL was achieved by preparing the plant extract stock solution in methanol. Ten concentrations ranging from 500 to 0.97 \u00b5g\/ml were obtained via dilutions. DPPH (1 mL) was combined with diluted solutions (1 mL each). At room temperature, the absorbance was measured at 517 nm after 30 minutes in the dark. Except for the extract, the control samples contained all of the essential reagents. The formula used to compute the percentage of inhibitions was:<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

A non-linear regression analysis was used to estimate the IC50\nvalues based on the curve representing the percentage inhibition vs.\nconcentration. The information was displayed as mean values (n = 3) \u00b1 standard\ndeviation. <\/p>\n\n\n\n

ABTS free radicals scavenging activity: <\/strong><\/p>\n\n\n\n

The ABTS radical cation removal of the color test was also used to\nmeasure the activity of plant materials to eliminate free radicals16<\/sup>. After mixing\n2.45 mM persulfate of potassium (1:1) with 7 mM ABTS in water, the ABTS cation\nradical was generated. The mixture was then left to rest for 16 hours in the\ndark at room temperature before being used. Then, methanol was added to the\nABTS+ solution to dilute it and achieved an absorbance of 0.7 \u00b10.02 at 734 nm.\nAfter 30 minutes following the first mixing, 3.995 mL of diluted ABTS\u00b7 solution\nwas then followed by 5 \u00b5L of plant extract, and the absorbance was measured.\nFor every assay, a suitable solvent blank was used. A minimum of three\nmeasurements were made for each. To find the percent of inhibition, the\nabsorbance at 734 nm- was measured and the following formula used was:<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

% of inhibition={(control Abs-sample Abs)\/(control Abs)}*100%<\/p>\n\n\n\n

where Am represents the absorbance of the ABTS radical with methanol and Ae represents the absorbance of the ABTS radical extract. In contrast, a non-linear regression model was used to determine the IC50 values based on the curve representing the percentage of inhibition vs. concentration. The information was displayed as mean values of triplet measurements \u00b1 standard deviation.<\/p>\n\n\n\n

Ferric reducing antioxidant power (FRAP)<\/strong><\/p>\n\n\n\n

Reduced antioxidant power due to ferric was assessed using\nspectrophotometry17<\/sup>. The process\nis based on reducing the colorless Fe3+<\/sup> TPTZ complex to the blue-colored\nFe2+<\/sup>-tripyridyltriazine complex, created at low pH by the action of\nantioxidants that donate electrons. This process was assessed by measuring an\nalteration in absorption at 593 nm. FRAP solution was prepared by mixing 10 mL\nTPTZ in 40 mM HCl, 20 mM FeCl3<\/sub>.6H2O, and 300 mM acetate buffer in a\n10:1:1 ratio at 37\u00b0C. Five microliters of the appropriately diluted plant\nsample and the newly prepared working FRAP reagent (3.995 mL) were pipetted and\nwell-mixed. After 30 min at  37\u00b0, the Fe3+<\/sup>\nTPTZ complex reduced to Fe2+<\/sup> and formed a bright blue color complex.\nComparing the absorption at 593 nm to a reagent blank, 3.995 mL of FRAP reagent\nand 5 \u00b5L of distilled water were used in place of the sample. Ascorbic acid\n(As) was used as a reference substance in the concentration range of 25-500\n\u00b5g\/mL. Ascorbic acid equivalents (AsE) for each gram of dried ivy extract were\nused to express FRAP activity results. The information was displayed as mean\nvalues of triplet measurements \u00b1 standard deviation.<\/p>\n\n\n\n

Inhibition of protein denaturation<\/strong><\/p>\n\n\n\n

Assay for Bovine Serum Albumin (BSA) denaturation using Williams et al<\/em>. (2008), a modified form of the BSA test18<\/sup>, the anti-inflammatory properties of both extracts of plants were assessed. Tris-buffered saline was used to create a 0.4% w\/v BSA solution.  Acetic acid was used to bring the pH down to 6.4. Stock solutions were prepared in methanol for each plant at 50 micrograms per ml, Many concentrations of one \u00b5g\/mL, 0.50 \u00b5g\/mL, and 0.25\u00b5g\/mL of the sample concentrations were reflected by equivalent aliquots of 5.0 \u00b5L, 10 \u00b5L, and 20 \u00b5L placed within test tubes that held one milliliter of 0.4%, w\/v BSA solution. The negative control (methanol) was also tested in this way. After that, the solutions were heated for 10 minutes at 72 \u00b0C in a water bath and then cooled for 20 minutes in a lab setting. Using an air blank, the solutions` turbidity (or degree of protein precipitation) was obtained at 660 nm in a (HITACHI U-5100 UV-VIS) spectrophotometer. The mean values for absorbance were recorded, and the experiments were run in duplicate. The equation was used to determine the percentage reduction in precipitation (protein denaturation) about the negative control: <\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Ointment formulation<\/strong><\/p>\n\n\n\n

As Paju et al<\/em>. (2013)19<\/sup> outlined, the conventional procedure was the basis for creating the medicated unguent formulation. Neobacin, a commercial ointment containing Bacitracin Zinc and Neomycin Sulphate (5 mg)was used as routine therapy. One gram of the extract and nineteen grams of white Vaseline were combined to create the medicated ointment. The 5% therapeutic ointment ingredients were all combined in a mortar and mortar, stirring continuously until the mixture was homogeneous and formed into an ointment preparation. To create an ointment without the therapeutic components. Before adding the mixture, the mortar was preheated for between five and six minutes at fifty degrees Celsius.<\/p>\n\n\n\n

Experimental animals <\/strong><\/p>\n\n\n\n

For the study, twenty adult albino rats of both sexes (weighing\n200\u2013250 grams) aged eight weeks were split into a total of four categories of\nfive rats each. Acquired from the Mutah University Science College’s Animal\nHouse, Biology Department. The animals were housed in different cages in\nrandomly assigned groups to monitor wound healing after a five-day\nacclimatization period. The animals were fed freely and had access to light for\ntwelve hours daily. The care and management of the animals adhered to globally\nrecognized standards for the ethical use of animals in laboratories, The\nPresent work was reviewed and approved by the institutional animal ethics\ncommittee (Decision number 2012021), as per the committee for supervision of\nin-vivo experimentations on animal guidelines in Mutah University.<\/p>\n\n\n\n

 Before creating the wound,\n70% ethanol had been applied as an antiseptic to the area that had been shaved.\nDiethyl ether was used to anesthetize the rats, and an electrical clipper\nremoved their hair. Applying a biopsy punch to remove an entire-thickness piece\nof skin from a pre-shaven region resulted in circular wounds that were 10 mm in\ndiameter. According to study20<\/sup>, no topical or\nsystemic antimicrobial medications were used, and the wounds were left\nuncovered. On the third day after the wounds had healed, the rats were divided\ninto four groups by randomization. Topically applied to the excised wounds were\nthe two prepared herbal ointments (leaves and fruits), positive (drug), and\nnegative (simple ointment alone) controls. Wounds were tracked to the four\ntherapy groups every three days starting on the third post-wounding day. Using\na digital vernier caliper, the wound diameters were measured, and the\ncontraction ratios of the wound were computed using 100% as the starting size. <\/p>\n\n\n\n

Where Di is the initial wound’s diameter while Df is the final wound diameter on the last day (day 12), <\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Statistical Analysis<\/strong><\/p>\n\n\n\n

Data analysis was performed using Microsoft Excel software (Windows\n10). Significant statistical differences were evaluated using a one-way\nanalysis of variance (ANOVA).<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

The maceration of 100 g of dried and powdered H. helix <\/em>leaves\nin a solution of 95% methanol for forty-eight hours yielded 4.27 g of dried raw\nextract. And 5.52g of dried raw extract was produced from 100 g of dried and\npowdered ripe H. helix <\/em>fruits that were macerated in 95% methanol for 48\nhours. <\/p>\n\n\n\n

Table 1 displays the examined samples`- total phenolic amount\n(TPC). The TPC, measured in terms of GAE, was 89.47 \u00b1 7.5 mg of GAE\/g of\nextract for H. helix <\/em>leaves and 100 \u00b1 7.64 mg of GAE\/g of extract for\nmature fruits. Trolox equivalents (mg) per gram of dry extract was the unit of\nmeasurement for total flavonoid content (TFC). The amounts of flavonoids in H.\nhelix<\/em>‘s leaves and mature fruits also differed greatly. With 37.14 \u00b11.3 mg\nof TE\/gm of extract, leaves had the highest flavonoid content, followed by ripe\nfruits with 27.61 \u00b1 0.2 mg of TE\/gm of extract.<\/p>\n\n\n\n

Another class of bioactive chemicals is known as total tannin\ncontent. Tannins in extracts should be considered despite their lower levels\nthan other bioactive ingredients. Table 1 expresses the overall tannin content\nof the different extracts. This investigation found the highest total tannin\nconcentration was 17.5 \u00b1 2.54 mg GAE\/g in ripe fruit extract and 24.79\u00b1 2.27 mg\nGAE\/g in leaf extract.  <\/p>\n\n\n\n

Regarding the DPPH measurement of antioxidant activity in each\nresearch extract, the extract, including ripe fruits, had the highest activity\n(IC50 3.49\u00b10.26 mg\/mL). In contrast, the leaves extract had the lowest value\n(IC50 8.79\u00b1 1.26 mg\/ml). Regarding ABTS antioxidant activity, the ripe fruit\nextract had a lower scavenging ability and higher IC50 values (8.7 \u00b1 1.85\nmg\/mL), but the leaf extract had a more significant scavenging activity\n(4.54\u00b10.99). Finally, the FRAP values indicate that the lower antioxidant\nproperties were similar to those of the DPPH scavenging experiment, which found\nthat the antioxidant activity of ripe fruit extracts was higher than that of\nleaf extracts; the IC50 values were 62.35\u00b1 4.41 and 75.5\u00b1 7.53, respectively.<\/p>\n\n\n\n

The current study compared the anti-inflammatory effects of mature\nfruits and leaves extracts to those of bovine serum albumin that had been\ndenatured In vitro<\/em>. Table 2 presents the findings. The current results\nshowed that both test extracts inhibited 50% of protein (albumin) denaturation\nin a dose-dependent manner at concentrations that ranged from 31.25 to 200\n\u03bcg\/ml. The IC50 values of 75.26\u00b1 3.87 and 115.62\u00b1 6.47 for the leaf and mature\nfruit extracts indicated that the leaf extract was more active.<\/p>\n\n\n\n

Table 1: Phytochemical content and total Yield of the Crude Extract of 95% methanol leaf extract and ripe fruit extract of H.helix<\/em><\/strong><\/p>\n\n\n\n\n\n\n\n
\n

 <\/p>\n<\/td>\n

\n

Polyphenol<\/strong><\/p>\n

GAE mg\/g extract<\/strong><\/p>\n<\/td>\n

\n

Flavonoid<\/strong><\/p>\n

TE mg\/g extract<\/strong><\/p>\n<\/td>\n

\n

Tannin<\/strong><\/p>\n

GAE mg\/g extract<\/strong><\/p>\n<\/td>\n

\n

Extract yield<\/strong><\/p>\n

% g\/100 g dry powder<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Leaves<\/strong><\/p>\n<\/td>\n

\n

89.47\u00b17.5<\/strong><\/p>\n<\/td>\n

\n

37.14\u00b11.3<\/strong><\/p>\n<\/td>\n

\n

24.79\u00b10.27<\/strong><\/p>\n<\/td>\n

\n

4.27 %<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Fruit<\/strong><\/p>\n<\/td>\n

\n

100\u00b17.64<\/strong><\/p>\n<\/td>\n

\n

27.61\u00b10.2<\/strong><\/p>\n<\/td>\n

\n

17.5\u00b10.54<\/strong><\/p>\n<\/td>\n

\n

5.52 %<\/strong><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 2: Antioxidant activity and anti-albumin denaturation activity of 95% methanol leaf extract and ripe fruit extract of H.helix<\/em> <\/strong><\/p>\n\n\n\n\n\n\n\n
\n

 <\/p>\n<\/td>\n

\n

ABTS<\/strong><\/p>\n

IC50  mg\/ml<\/strong><\/p>\n<\/td>\n

\n

DPPH<\/strong><\/p>\n

IC50  mg\/ml<\/strong><\/p>\n<\/td>\n

\n

FRAP<\/strong><\/p>\n

AscE  mg\/g<\/strong><\/p>\n<\/td>\n

\n

albumin denaturation<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Leaves<\/p>\n<\/td>\n

\n

4.54\u00b1 0.99<\/p>\n<\/td>\n

\n

8.79\u00b11.26<\/p>\n<\/td>\n

\n

62.35\u00b1 4.41<\/p>\n<\/td>\n

\n

75.26\u00b13.87<\/p>\n<\/td>\n<\/tr>\n

\n

Fruit<\/p>\n<\/td>\n

\n

8.696 \u00b1 1.85<\/p>\n<\/td>\n

\n

3.49\u00b1 0.65<\/p>\n<\/td>\n

\n

75.5\u00b17.53<\/p>\n<\/td>\n

\n

115.62\u00b16.47<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 3: Effect of 95% methanol leaf extract and ripe fruit extract of H.helix <\/em>on wound contraction in excision model<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
\n

Treatment day<\/strong><\/p>\n<\/td>\n

\n

-ve group<\/strong><\/p>\n

Pure Ointment<\/strong><\/p>\n<\/td>\n

\n

5% Ointment Leaves<\/strong><\/p>\n<\/td>\n

\n

5% Ointment fruit<\/strong><\/p>\n<\/td>\n

\n

Drug<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

3<\/p>\n<\/td>\n

\n

21.64<\/p>\n<\/td>\n

\n

14.12<\/p>\n<\/td>\n

\n

10.47<\/p>\n<\/td>\n

\n

16.51<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/p>\n<\/td>\n

\n

30,4<\/p>\n<\/td>\n

\n

46.29<\/p>\n<\/td>\n

\n

43.42<\/p>\n<\/td>\n

\n

33.96<\/p>\n<\/td>\n<\/tr>\n

\n

9<\/p>\n<\/td>\n

\n

52.13<\/p>\n<\/td>\n

\n

62.78<\/p>\n<\/td>\n

\n

68.31<\/p>\n<\/td>\n

\n

68.64<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

81.12<\/p>\n<\/td>\n

\n

95.82<\/p>\n<\/td>\n

\n

90.21<\/p>\n<\/td>\n

\n

86.43<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 1:<\/strong> In the excision model, the wound contraction progressed during the post-wounding days (A) negative control applying basic ointment, (B) 5% ointment leaves, (C) 5% ointment fruit, and (D) <\/strong>Neobacin<\/strong> ointment<\/strong>.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 2:<\/strong> Percentage of wound area contraction effects in mice in excision mode, in vivo<\/em> study(A) negative control applying basic ointment, (B) 5% ointment leaves,  (C) 5% ointment fruit, and (D) <\/strong>Neobacin<\/strong> ointment<\/strong>.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

Research concerning plant varieties’ antioxidant properties has\nexploded in recent years due to the use of several of them as sources of\nphytotherapeutic compounds21\u201323<\/sup>. Some of these\nmethods include preventing oxidative stress, limiting reactive oxygen species\n(ROS) to safe levels24,25<\/sup>, and using\nthem for effective signaling. Studying the antioxidant properties of plant\nspecies is essential because secondary metabolites, especially phenols, can\nchange the amount of reactive oxygen species (ROS) and start a chain of\nmetabolic reactions that promote tolerance. Because of their aromatic ring,\nwhich stabilizes and repositions the unpaired electrons in their structure to\nallow for the exchanging of hydrogen atoms and electrons to their hydroxyl\ngroups, phenols are the main compounds in plants that show antioxidant activity26,27<\/sup>. The total\nphenol content is influenced by temperature, water stress, light conditions,\nplant tissue, developmental stage, and other environmental factors28,29<\/sup>.<\/p>\n\n\n\n

H. helix<\/em>‘s phytochemical screening revealed the presence of many kinds of\nsecondary metabolites, including tannins, terpenoids, alkaloids, and saponins.\nAlkaloids were detected throughout the methanol, n-hexane, chloroform, and\nethyl acetate extracts, whilst tannins, terpenoids, and saponins were found in\nthe chloroform and methanolic extracts30<\/sup>. \u03b2-amyrin,\nstigmasterol, and hexadecanoic acid were identified as the active ingredients\nin H. helix <\/em>leaves extract extracted by methylene chloride31<\/sup>.\nChromatographic techniques were used to identify the flavonoids quercetin,\nkaempferol, apigenin, and rutin32<\/sup>. With the use\nof reversed-phase high-HPLC, the saponins \u03b1-hederin and hederacoside C from\nvarious ivy leaf extracts were identified33<\/sup>.<\/p>\n\n\n\n

The study relied on this information to compare the effects of the\nripe H.helix <\/em>fruit extract and the H. helix <\/em>leaf extract. While\nripe ivy leaves have been the subject of numerous studies, as far as we know,\nnone of them have examined the significance of ripe H. helix <\/em>fruits in\nwound healing.<\/p>\n\n\n\n

The investigators are now utilizing a variety of antioxidant tests\nto find the antioxidant potential in natural extracts. More than a single\nexperiment is required to measure the antioxidant capacity of natural extracts\ndue to the complex structure of the bioactive chemicals present3,34,35<\/sup>. However,\nDPPH, ABTS, and FRAP are the most commonly utilized techniques36<\/sup>. Using\nphenolic compounds with antioxidant activity is preferable when creating\npharmaceutical formulations from any natural resource5,37<\/sup>. Several\nstudies have supported the link between phenolic chemicals and antioxidant\ncapability38,39<\/sup>. Table 2 shows\nthe antioxidant potential of many different extracts that exhibit different\nantioxidant properties from one another. Phenolic compounds are among the main\nchemical classes that are known to act as principal antioxidants or harmful\nfree radical terminators.<\/p>\n\n\n\n

 These earlier results\nsuggest that any of the techniques employed in this investigation can determine\nand categorize the antioxidant activity of these different extracts. According\nto study40<\/sup>, wound healing\nis a complicated process that begins during the fibroblastic phase, when the\nwound’s surrounding tissue begins to shrink, and concludes with the cellular\nstructures and layers of tissue of wounded tissue being returned to their\ninitial state. Contracture, granulation, epithelization, and collagenation are\nsome of its stages41<\/sup>. The\ntherapeutic benefits of herbal treatments are mostly caused by a variety of\ncircumstances. Because polyphenolic compounds may control and modify inflammatory\nreactions, they are useful as therapeutic agents in the healing of wounds. By\npromoting fibroblast proliferation and\/or collagen formation, a variety of\nphytochemicals found in medicinal plants are significant regulators of\nhomeostasis, re-epithelialization, and regeneration. Many studies have shown\nthat medicinal plants and the phytochemicals they contain have a potent effect\non wound healing through several interconnected pathways42,43<\/sup>.<\/p>\n\n\n\n

There are three stages of wound healing: the inflammatory,\nproliferative, and maturational\/remodeling phases. Collagen deposition, angiogenesis,\nand epithelialization occur after the proliferative phase.<\/p>\n\n\n\n

It is well known that wound healing throughout the regeneration\nprocess requires the carefully regulated presence of defense cells44,45<\/sup>. Inflammation\nand hemostasis are the distinctive characteristics of the inflammatory phase.\nSo, controlling inflammation is the beginning of treating wounds without\ncausing scarring. Significant alterations were validated by the examination of\ndata obtained from polymorphonuclear cells. In the chronic stage, the H.\nhelix <\/em>extract first decreases the number of polymorphonuclear cells and\nthen encourages the exchange of polymorphonuclear cells, which is essential for\nthe completion of the regenerative and inflammatory mechanisms46<\/sup>.<\/p>\n\n\n\n

According to G\u00fcl\u00e7in et al. (2004)47<\/sup>, H. helix <\/em>constituents\nsuch as \u03b1-hederin completely drain intracellular glutathione during In vitro<\/em>\ntests, hence preventing the generation of oxygen species that are reactive\n(ROS). Therefore, a decrease in nitric oxide release leads to a decrease in the\nNF-kappa B expression, the transcription factor of inflammatory cytokines\n(e.g., IL1-\u03b2, TNF-\u03b1), and the chemokines that cause the migration of\ninflammatory cells34<\/sup>. This\nindicates that the H. helix <\/em>extract can function in both\npolymorphonuclear migration control and reducing the activation of macrophages.\nReduced visible scar tissue results from wounds contracting throughout the\nmaturation48<\/sup>. The\ngranulation tissue that develops at the end of the proliferative phase mainly\ncomprises new tiny blood vessels, fibroblasts, collagen, and edema. These\nphytochemical ingredients powerfully and efficiently prevent the release or\naction of prostaglandin and bradykinin during the third stage of edema\nproduction. Its secondary metabolites may contribute to its anti-inflammatory\nproperties. Terpenoids prevent the metabolism of arachidonic acid and decrease\nthe activity of phospholipase A249,50<\/sup>. Also,\nTerpenoids help wounds heal by having antibacterial and astringent abilities\nthat seem to have been the cause of wound contraction and an increased rate of\nepithelial development25,51<\/sup>. <\/p>\n\n\n\n

Fibroblasts relocate to the wound site throughout the healing\nprocess, where they proliferate and go on to create collagen, the primary\nextracellular matrix component. Fibroblast stimulation is one of the ways that\nherbal extracts may speed up the healing of wounds. Put differently, some\nphytochemicals stimulate the growth, migration, and activity of fibroblasts52,53<\/sup>. The lifespan\nof collagen fibrils will rise with any medication that suppresses these\nprocesses. Therefore, by increasing the antioxidant state, several herbal\nextracts promote improved collagenation54<\/sup>. Several\nresearchers have acknowledged that antioxidants can influence the process of\noxidation by their ability to scavenge oxygen, chelate catalytic metals, and\nreact with free radicals. It is believed that reactive oxygen species (ROS) and\nfree radicals play a significant role in impeding the healing process20<\/sup>. Research has\ndemonstrated the antioxidant properties of terpenoids30<\/sup>, flavonoids55<\/sup>, tannins56,57<\/sup>, and saponins58<\/sup>. The existence\nof saponins with antioxidant activities that are isolated from the H. helix <\/em>has\nbeen shown, such as hederacolchisides E and F, \u03b1-hederin, and hederasaponin-c47<\/sup>. In addition,\nit is well known that flavonoids and their derivatives inhibit the death of\ncells by increasing vascularity and reducing lipid peroxidation. By blocking\nprostaglandin formation, polyphenols and flavonoids have antimicrobial and\nanti-inflammatory properties28<\/sup>. Glycosides\nhave anti-inflammatory, antibacterial, and antioxidant properties. Because of\ntheir astringent and antioxidant qualities, tannins improve the efficiency and\ndevelopment of new tissue, speeding up the wound recovery process. It is\ntherefore plausible that the phytochemical component present in the raw extract\npromotes wound healing59,60<\/sup>. Applying\nplant extracts and components topically onto a wound will not cause the plant\nto produce the desired effect, to ensure a sustained release of the medication,\nit is necessary to apply ointment at the site of application. The ointment’s\nbase facilitated the formation of a moisture barrier across the wound region,\nmainly due to the presence of hard, white, and soft paraffin in large part49<\/sup>.<\/p>\n\n\n\n

 The findings of the excision\nmodel demonstrated that each extract significantly promoted wound healing. <\/p>\n\n\n\n

Comparatively, various plants with compositions similar to those of\nH. helix<\/em>, which has anti-inflammatory and wound-healing characteristics,\nhave also been seen and described in analogous ways during these situations61\u201363<\/sup>. <\/p>\n\n\n\n

Quercetin, kaempferol, glucosides, epicatechin, and catechin are\nthe principal chemicals found in leaves that are recognized as wound-healing\nagents64<\/sup>. Also,\npunicalin, kaempferol, quercetin-3-O-xylopyranoside, Punicalagin, quercitrin,\nand ellagic acid, were found in the plant, also,65<\/sup> reported that\nthese compounds may be linked to better cell proliferation,\nre-epithelialization, and the remodeling phase of wounds, as many types of\nresearch had shown that the presence of these components in H. helix <\/em>extract\nThis can explain the healing of wounds in samples treated with extracts in less\ntime than untreated samples. <\/p>\n\n\n\n

Conclusions<\/strong><\/p>\n\n\n\n

 The study conducted\nhighlights the antioxidant, anti-inflammatory, and wound-healing qualities\nof extracts from H.<\/em> helix<\/em> ripe fruits and leaves. This\ntraditional herbal medicine has piqued the interest of researchers as it can be\nused to treat various illnesses. The findings could inspire the pharmaceutical\nindustry to develop treatments using these plant extracts and encourage the use\nof these natural products in an ecologically and socioeconomically sustainable\nway. The revealed bioactive components of the extracts include\nflavonoids, phenolic ingredients, and tannins, which could be responsible for the abovementioned healing\nbenefits. Therefore, it can be inferred that H. helix’s<\/em> healing\npotential can have benefits for both medicinal and cosmetic applications.<\/p>\n\n\n\n

Acknowledgemet <\/strong><\/p>\n\n\n\n

None to declare<\/p>\n\n\n\n

Conflict of Interest <\/strong> <\/p>\n\n\n\n

The author declares no conflict of interest. <\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

No external funding for this study.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. Okba MM, Baki PMA, Abu-Elghait M, et al. UPLC-ESI-MS\/MS profiling of the underground parts of common Iris species in relation to their anti-virulence activities against Staphylococcus aureus. J Ethnopharmacol<\/em>. 2022;282:114658.
    CrossRef<\/a><\/li>
  2. Ramadan A, Kamel G, Shokry AA, El-Shiekh RA. Tropical Journal of Natural Product Research.”. Published online 2020.
    CrossRef <\/li>
  3. Sen NB, Guzelmeric E, Vovk I, Glavnik V, K\u0131rm\u0131z\u0131bekmez H, Yesilada E. Phytochemical and bioactivity studies on Hedera helix L.(ivy) flower pollen and ivy bee pollen. Antioxidants<\/em>. 2023;12(7):1394.
    CrossRef <\/a><\/li>
  4. Rashed KNZ. Comparsion of Antioxidant Potential of Dimocarpus Longan Lour. Extracts and the main Phytoconstituents. Int J Sci Invent Today<\/em>. 2013;2(6):487-491.<\/li>
  5. Shokry A, El-Shiekh R, Kamel G, Ramadan A. Phytochemical contents, biological activities and therapeutic applications of hedera helix (ivy leaf) extracts: a review. Nat Prod J<\/em>. 2022;12(4):22-32.
     CrossRef <\/a><\/li>
  6. Parvu M, Vlase L, Parvu AE, Rosca-Casian O, Gheldiu AM, Parvu O. Phenolic compounds and antifungal activity of Hedera helix L.(Ivy) flowers and fruits. Not Bot Horti Agrobot Cluj-Napoca<\/em>. 2015;43(1):53-58.
    CrossRef <\/a><\/li>
  7. V\u00f6lp A, Schmitz J, Bulitta M, Raskopf E, Acikel C, M\u00f6sges R. Ivy leaves extract EA 575 in the treatment of cough during acute respiratory tract infections: meta-analysis of double-blind, randomized, placebo-controlled trials. Sci Rep<\/em>. 2022;12(1):20041.
     CrossRef <\/a><\/li>
  8. Yenig\u00fcn VB, Kocyigit A, Kan\u0131mdan E, Durmus E, Koktasoglu F. Hedera helix (Wall Ivy) leaf ethanol extract shows cytotoxic and apoptotic effects in glioblastoma cells by generating reactive oxygen species. Acta Medica Cordoba<\/em>. 2023;54(4):295-303.
     CrossRef <\/a><\/li>
  9. Khan S, Adil A, Naeem S, et al. Evaluation of Acute and Chronic Antidiabetic Activity of Ivy (Hedera helix L.) Aqueous Leaf Extract in Rat Model. Pak J Biol Sci<\/em>. 2020;23(11):1357-1368.
     CrossRef <\/a><\/li>
  10. Erdogdu M, Atilgan A, Erdogdu Y, Yildiz A. Flavonoid from Hedera helix fruits: A promising new natural sensitizer for DSSCs. J Photochem Photobiol A Chem<\/em>. 2024;448:115288.
     CrossRef <\/a><\/li>
  11. Vl S. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods Enzymol<\/em>. 1999;299:152-178.
     CrossRef <\/a><\/li>
  12. Ordonez AAL, Gomez JD, Vattuone MA. Antioxidant activities of Sechium edule (Jacq.) Swartz extracts. Food Chem<\/em>. 2006;97(3):452-458.
     CrossRef <\/a><\/li>
  13. Galv\u00e3o MAM, Arruda AO de, Bezerra ICF, Ferreira MRA, Soares LAL. Evaluation of the Folin-Ciocalteu method and quantification of total tannins in stem barks and pods from Libidibia ferrea (Mart. ex Tul) LP Queiroz. Brazilian Arch Biol Technol<\/em>. 2018;61:e18170586.
     CrossRef <\/a><\/li>
  14. Kumarasamy Y, Byres M, Cox PJ, Jaspars M, Nahar L, Sarker SD. Screening seeds of some Scottish plants for free radical scavenging activity. Phyther Res An Int J Devoted to Pharmacol Toxicol Eval Nat Prod Deriv<\/em>. 2007;21(7):615-621.
     CrossRef <\/a><\/li>
  15. Altarawneh RM, Al\u2010Jaafreh AM, Qaralleh H, Al\u2010Qaralleh OS. Chemical profiling of Punica granatum peels from Jordan using LC\u2013MS\/MS and study on their biological activities. Int J Food Sci Technol<\/em>. 2022;57(8):5256-5267.
     CrossRef <\/a><\/li>
  16. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med<\/em>. 1999;26(9-10):1231-1237.
     CrossRef <\/a><\/li>
  17. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of \u201cantioxidant power\u201d: the FRAP assay. Anal Biochem<\/em>. 1996;239(1):70-76.
    CrossRef <\/a><\/li>
  18. Williams LAD, O\u2019connar A, Latore L, et al. The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals. West Indian Med J<\/em>. 2008;57(4).<\/li>
  19. Paju N, Yamlean PVY, Kojong N. Uji efektivitas salep ekstrak daun binahong (Anredera cordifolia (Ten.) Steenis) pada kelinci (Oryctolagus cuniculus) yang terinfeksi bakteri Staphylococcus aureus. Pharmacon<\/em>. 2013;2(1).<\/li>
  20. Cedillo-Cortezano M, Martinez-Cuevas LR, L\u00f3pez JAM, Barrera L\u00f3pez IL, Escutia-Perez S, Petricevich VL. Use of Medicinal Plants in the Process of Wound Healing: A Literature Review. Pharmaceuticals<\/em>. 2024;17(3):303.
     CrossRef <\/a><\/li>
  21. Manilal A, Sabu KR, Shewangizaw M, et al. In vitro antibacterial activity of medicinal plants against biofilm-forming methicillin-resistant Staphylococcus aureus: efficacy of Moringa stenopetala and Rosmarinus officinalis extracts. Heliyon<\/em>. 2020;6(1).
     CrossRef <\/a><\/li>
  22. Ghildiyal S, Gautam MK, Joshi VK, Goel RK. Wound healing and antimicrobial activity of two classical formulations of Laghupanchamula in rats. J Ayurveda Integr Med<\/em>. 2015;6(4):241.
     CrossRef <\/a><\/li>
  23. Karumi EW, Maitai CK, Okalebo FA, et al. Anthelmintic and antibacterial activity of Hagenia abyssinica (Bruce) JF Gmel (rosaceae). East Cent African J Pharm Sci<\/em>. 2013;16(3):75-80.<\/li>
  24. Mechesso AF, Tadese A, Tesfaye R, Tamiru W, Eguale T. Experimental evaluation of wound healing activity of Croton macrostachyus in rat. African J Pharm Pharmacol<\/em>. 2016;10(39):832-838.
     CrossRef <\/a><\/li>
  25. Hossain MA, AL-Raqmi KAS, Al-Mijizy ZH, Weli AM, Al-Riyami Q. Study of total phenol, flavonoids contents and phytochemical screening of various leaves crude extracts of locally grown Thymus vulgaris. Asian Pac J Trop Biomed<\/em>. 2013;3(9):705-710.
     CrossRef <\/a><\/li>
  26. Zeng Q, Xie H, Song H, et al. In vivo wound healing activity of Abrus cantoniensis extract. Evidence-Based Complement Altern Med<\/em>. 2016;2016.
     CrossRef <\/a><\/li>
  27. Upadhyay A, Chattopadhyay P, Goyary D, Mitra Mazumder P, Veer V. Ixora coccinea enhances cutaneous wound healing by upregulating the expression of collagen and basic fibroblast growth factor. Int Sch Res Not<\/em>. 2014;2014.
     CrossRef <\/a><\/li>
  28. Sharma RK, Kundra R, Samant SS, Nandi SK. Antioxidant properties of methanol extracts from Olea ferruginea Royle seeds. Natl Acad Sci Lett<\/em>. 2017;40:379-382.
     CrossRef <\/a><\/li>
  29. Diljkan M, \u0160kondri\u0107 S, Hasanagi\u0107 D, et al. The antioxidant response of Hedera helix leaves to seasonal temperature variations. Bot Serbica<\/em>. 2022;46(2):295-309.
     CrossRef <\/a><\/li>
  30. Ndezo Bisso B, Njikang Epie Nkwelle R, Tchuenguem Tchuenteu R, Dzoyem JP. Phytochemical screening, antioxidant, and antimicrobial activities of seven underinvestigated medicinal plants against microbial pathogens. Adv Pharmacol Pharm Sci<\/em>. 2022;2022.
     CrossRef <\/a><\/li>
  31. Medeiros JR, Medeiros H, Mascarenhas C, Davin LB, Lewis NG. Bioactive components of Hedera helix. Published online 2002.<\/li>
  32. Ferrara L, Naviglio D, Faralli S. Identification of active principles of Hedera helix L. in aqueous extracts. J Phytochem<\/em>. 2013;114:170-175.<\/li>
  33. Demirci B, Goppel M, Demirci F, Franz G. HPLC profiling and quantification of active principles in leaves of Hedera helix L. Die Pharm Int J Pharm Sci<\/em>. 2004;59(10):770-774.<\/li>
  34. Shokry AA, El-Shiekh RA, Kamel G, Bakr AF, Ramadan A. Bioactive phenolics fraction of Hedera helix L.(Common Ivy Leaf) standardized extract ameliorates LPS-induced acute lung injury in the mouse model through the inhibition of proinflammatory cytokines and oxidative stress. Heliyon<\/em>. 2022;8(5).
     CrossRef <\/a><\/li>
  35. Suica-Bunghez IR, SORESCU AA, DONCEA SM, Constantin M, Raut I, Rodica Mariana ION. Phytochemical, antioxidant and antimicrobial characterization of Hedera helix L. extract. J Plant Dev<\/em>. 2020;27.
    CrossRef <\/a><\/li>
  36. Qabaha K, Abbadi J, Yaghmour R, Hijawi T, Naser SA, Al-Rimawi F. Unveiling the antibacterial and antioxidant potential of Hedera helix leaf extracts: recent findings. Can J Physiol Pharmacol<\/em>. 2023;102(1):26-32.
     CrossRef <\/a><\/li>
  37. Gavrila AI, Zalaru CM, Tatia R, et al. Green Extraction Techniques of Phytochemicals from Hedera helix L. and In Vitro Characterization of the Extracts. Plants<\/em>. 2023;12(22):3908.
     CrossRef <\/a><\/li>
  38. Punia S, Sandhu KS. FUNCTIONAL AND ANTIOXIDANT PROPERTIES OF DIFFERENT MILLING FRACTIONS OF INDIAN BARLEY CULTIVARS. Carpathian J Food Sci Technol<\/em>. 2015;7(4).<\/li>
  39. Sandhu KS, Godara P, Kaur M, Punia S. Effect of toasting on physical, functional and antioxidant properties of flour from oat (Avena sativa L.) cultivars. J Saudi Soc Agric Sci<\/em>. 2017;16(2):197-203.
     CrossRef <\/a><\/li>
  40. Yadav JP, Verma A, Pathak P, Kumar V, Patel DK. Wound healing, antidiabetic and antioxidant activity of Neolamarckia cadamba, quercetin rich, extract. Pharmacol Res Chinese Med<\/em>. 2024;11:100417.
     CrossRef <\/a><\/li>
  41. Wild T, Rahbarnia A, Kellner M, Sobotka L, Eberlein T. Basics in nutrition and wound healing. Nutrition<\/em>. 2010;26(9):862-866.
     CrossRef <\/a><\/li>
  42. Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol<\/em>. 2015;54(7):740-751.
    CrossRef <\/a><\/li>
  43. Artem Ataide J, Caramori Cefali L, Machado Croisfelt F, Arruda Martins Shimojo A, Oliveira\u2010Nascimento L, Gava Mazzola P. Natural actives for wound healing: A review. Phyther Res<\/em>. 2018;32(9):1664-1674.
     CrossRef <\/a><\/li>
  44. Gepdiremen A, Mshvildadze V, S\u00fcleyman H, Elias R. Acute and chronic antiinflammatory effects of Hedera colchica in rats. J Ethnopharmacol<\/em>. 2004;94(1):191-195.
     CrossRef <\/a><\/li>
  45. de Moraes Palma FA, da Mata AR, de Almeida Rocha I, et al. Study of wound healing in rat skin treated with extract of Hedera helix, L. Brazilian J Dev<\/em>. 2021;7(12):115126-115139.
     CrossRef <\/a><\/li>
  46. Vieira AE, Repeke CE, Ferreira Junior S de B, et al. Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization. PLoS One<\/em>. 2015;10(5):e0128021.
     CrossRef <\/a><\/li>
  47. G\u00fcl\u00e7in \u0130, Mshvildadze V, Gepdiremen A, Elias R. Antioxidant activity of saponins isolated from ivy: \u03b1-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F. Planta Med<\/em>. 2004;70(06):561-563.
    CrossRef <\/a><\/li>
  48. Phillips GD, Whitehead RA, Knighton DR. Initiation and pattern of angiogenesis in wound healing in the rat. Am J Anat<\/em>. 1991;192(3):257-262.
     CrossRef <\/a><\/li>
  49. Mekonnen A, Sidamo T, Asres K, Engidawork E. In vivo wound healing activity and phytochemical screening of the crude extract and various fractions of Kalanchoe petitiana A. Rich (Crassulaceae) leaves in mice. J Ethnopharmacol<\/em>. 2013;145(2):638-646.
     CrossRef <\/a><\/li>
  50. Gebrehiwot M, Asres K, Bisrat D, Mazumder A, Lindemann P, Bucar F. Evaluation of the wound healing property of Commiphora guidottii Chiov. ex. Guid. BMC Complement Altern Med<\/em>. 2015;15(1):1-11.
     CrossRef <\/a><\/li>
  51. Ugochukwu SC, Arukwe Uche I, Ifeanyi O. Available online at www. pelagiaresearchlibrary. com. Asian J Plant Sci Res<\/em>. 2013;3(3):10-13.<\/li>
  52. Amin ZA, Ali HM, Alshawsh MA, Darvish PH, Abdulla MA. Application of Antrodia camphorata promotes rat\u2019s wound healing in vivo and facilitates fibroblast cell proliferation in vitro. Evidence-Based Complement Altern Med<\/em>. 2015;2015.
     CrossRef <\/a><\/li>
  53. Bueno FG, Panizzon GP, de Leite Mello EVS, et al. Hydrolyzable tannins from hydroalcoholic extract from Poincianella pluviosa stem bark and its wound-healing properties: phytochemical investigations and influence on in vitro cell physiology of human keratinocytes and dermal fibroblasts. Fitoterapia<\/em>. 2014;99:252-260.
     CrossRef <\/a><\/li>
  54. Umadevi S, Mohanta G, Kalaichelvan V, Manavalan R. Studies on wound healing effect of Flaveria trinervia leaf in mice. Indian J Pharm Sci<\/em>. 2006;68(1).
    CrossRef <\/a><\/li>
  55. Ghasemzadeh A, Jaafar HZE, Rahmat A, Ashkani S. Secondary metabolites constituents and antioxidant, anticancer and antibacterial activities of Etlingera elatior (Jack) RM Sm grown in different locations of Malaysia. BMC Complement Altern Med<\/em>. 2015;15:1-10.
     CrossRef <\/a><\/li>
  56. Jain S, Jain A, Jain S, Malviya N, Jain V, Kumar D. Estimation of total phenolic, tannins, and flavonoid contents and antioxidant activity of Cedrus deodara heart wood extracts. Egypt Pharm J<\/em>. 2015;14(1):10-14.
     CrossRef <\/a><\/li>
  57. Costa G, Gonz\u00e1lez-Manzano S, Gonz\u00e1lez-Param\u00e1s A, Figueiredo IV, Santos-Buelga C, Batista MT. Flavan hetero-dimers in the Cymbopogon citratus infusion tannin fraction and their contribution to the antioxidant activity. Food Funct<\/em>. 2015;6(3):932-937.
     CrossRef <\/a><\/li>
  58. Nadeem A, Shahzad H, Ahmed B, Muntean T, Waseem M, Tabassum A. Phytochemical profiling of antimicrobial and potential antioxidant plant: Nepeta cataria. Front Plant Sci<\/em>. 2022;13:969316.
     CrossRef <\/a><\/li>
  59. Mulisa E, Asres K, Engidawork E. Evaluation of wound healing and anti-inflammatory activity of the rhizomes of Rumex abyssinicus J.(Polygonaceae) in mice. BMC Complement Altern Med<\/em>. 2015;15(1):1-10.
     CrossRef <\/a><\/li>
  60. Lin PH, Sermersheim M, Li H, Lee PHU, Steinberg SM, Ma J. Zinc in wound healing modulation. Nutrients<\/em>. 2017;10(1):16.
     CrossRef <\/a><\/li>
  61. Lopes AI, Pintado MM, Tavaria FK. Plant-Based Films and Hydrogels for Wound Healing. Microorganisms<\/em>. 2024;12(3):438.
    CrossRef <\/a><\/li>
  62. Paswan SK, Verma P, Mohapatra L, Rao CV, Srivastava S, Kumar S. Assessment of wound healing activity and safety profile of Amaranthus spinosus extract using incision wound healing model. Curr Res Biotechnol<\/em>. 2023;6:100151.
     CrossRef <\/a><\/li>
  63. Yuniarsih N, Hidayah H, Gunarti NS, et al. Evaluation of Wound-Healing Activity of Hydrogel Extract of Sansevieria trifasciata Leaves (Asparagaceae). Adv Pharmacol Pharm Sci<\/em>. 2023;2023.
     CrossRef <\/a><\/li>
  64. Fujishima MAT, S\u00e1 DMC, Lima CM de S, et al. Chemical profiling of Curatella americana Linn leaves by UPLC-HRMS and its wound healing activity in mice. PLoS One<\/em>. 2020;15(1):e0225514.
    CrossRef <\/a><\/li>
  65. Pereira LOM, Vilegas W, Tangerina MMP, et al. Lafoensia pacari A. St.-Hil.: Wound healing activity and mechanism of action of standardized hydroethanolic leaves extract. J Ethnopharmacol<\/em>. 2018;219:337-350.
     CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

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