{"id":60445,"date":"2024-09-30T11:32:33","date_gmt":"2024-09-30T11:32:33","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=60445"},"modified":"2024-10-09T18:02:08","modified_gmt":"2024-10-09T18:02:08","slug":"the-strong-effect-of-propolis-in-suppressing-nf-%ce%bab-cysc-and-ace2-on-a-high-fat-diet","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no3\/the-strong-effect-of-propolis-in-suppressing-nf-%ce%bab-cysc-and-ace2-on-a-high-fat-diet\/","title":{"rendered":"The Strong Effect of Propolis in Suppressing NF-\u03baB, CysC, and ACE2 on a High-fat Diet"},"content":{"rendered":"\n

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

Obesity is found in adults, adolescents\nand children. Over 1.9 billion adults worldwide are overweight, and over 650\nmillion adults are obese. According to the WHO, obesity results in the death of\n2.8 million adults annually.1<\/sup> Nationally, data from the\n2018 National Health Research (Riskesnas) of Indonesia showed that 26.6 percent\nof the adult population aged over 18 years had central obesity and shows a\nrapid increase from 2007 where the population experiencing central obesity\nreached 18.8 percent. South Sulawesi, Indonesia is one of 18 provinces with the\nhighest prevalence of central obesity.2<\/sup> <\/p>\n\n\n\n

One of the dominant causes of obesity is a high fat\ndiet, where the amount of a high fat diet correlates strongly with the degree\nof obesity.3<\/sup> Obesity contributes to the risk for several diseases,\nsuch as cancer, metabolic syndrome, cardiovascular disease, hypertension, and\ndiabetes, and decreases the body’s defenses and immune system.4<\/sup> and\nis a major contributor to the risk of kidney diseases, such as chronic kidney\ndisease (CKD).5,6<\/sup> <\/p>\n\n\n\n

Metabolic diseases caused by stress and dysfunction of\ntissues are strongly associated with obesity. Obesity can cause the body to\nreact in various ways, such as producing more T helper 1 and 17, which in turn\ntrigger the inflammatory process by producing proinflammatory cytokines like\nIL6, IL-2, and IFN\u03b3.7,8<\/sup>  <\/p>\n\n\n\n

By increasing metabolic rate and renal tubular\nreabsorption, obesity may increase the possibility of developing CKD in its\nearliest phases. This results in compensatory renal vasodilatation, glomerular\nhyperfiltration, elevated glomerular capillary pressure, and glomerular\nhypertrophy. Although the altered renal hemodynamics and increased glomerular\nfiltration rate (GFR) initially compensate the increased tubular reabsorption\nand allowed a balance between salt and water intake and output, which must be\nmaintained, gradually increasing mechanical stress on the glomerular capillaries\nmay lead to slow injury development.9,10<\/sup> <\/p>\n\n\n\n

Several studies have been done in traditional herbal\nmedicine including Propolis.11,12,13,14,15,16,17,18 <\/sup> Propolis is useful in the world of health with\nvarious therapeutic effects including anti-inflammatory, antioxidant,\nanticarcinogenic, antibacterial, antifungal, antiprotozoal, antiviral,\nantidiabetic.19,20<\/sup>\nFlavonoids are one of the main compounds involved in this function.21<\/sup>\nSeveral previous studies on the compounds found in propolis have yielded\nsimilar levels of accuracy in identifying the presence of phenolic compounds in\npropolis using the HPLC-MS\/MS and HPLC-UV methods.22<\/sup> Similarly, the\nliterature has described a few of propolis’s biological activities as well as\nthose of its isolated compounds.23<\/sup><\/p>\n\n\n\n

Furthermore, an evaluation of the potential bioactive\ncompounds and antioxidant activity of propolis which contains phenolic and\nflavonoid compounds has been carried out. The results showed a high total\nphenolic and flavonoid content.24<\/sup> Fifty-nine phenolic compounds were\nfound and quantified in the hydroalcoholic propolis extract using a novel\ntargeted HPLC-PDA-ESI\/MS method, which also demonstrated the antioxidant\nactivity of propolis samples.25<\/sup><\/p>\n\n\n\n

Analysis of phenolic compounds (flavonoids and\nphenolic acid derivatives) in propolis using HPLC-MS\/MS is the main active\nconstituent of the propolis resin fraction and Propolis ethanol extracts from\nSpain, Argentina and Italy indicate approximately the same total ion\nchromatogram (TIC) profile, according to an analysis of flavonoids from\npropolis using online HPLC-electrospray mass spectrometry.26.27<\/sup>\nOverall, several previous studies show that phenolic compounds and their\nderivatives are the main active components of propolis.<\/p>\n\n\n\n

Propolis has also been proven to be a potential anti-inflammatory agent and an agent for reducing the production of free radicals so it is thought to be useful for treating inflammatory diseases.28<\/sup> In in vivo tests to see the benefits of propolis on the respiratory system in mice’s defence against cigarette smoke and propolis administration was found to be able to restore the levels of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, and catalase, as well as biochemical markers of inflammation and oxidative stress such as nitrite and myeloperoxidase.29<\/sup> <\/p>\n\n\n\n

NF-\u03baB is a key player in the regulation of\ninflammation and has been linked to metabolic abnormalities like obesity.30<\/sup> NF-\u03baB achieves\nthis by encouraging the production of several pro-inflammatory genes. As a\nwell-studied modulator of inflammation and immunity, the NF-\u03baB pathway relates\nthe inflammatory and metabolic responses in obesity and serves as a starting\npoint for a more comprehensive understanding of metabolic disorders and the\ndevelopment of novel therapeutic approaches.31<\/sup><\/p>\n\n\n\n

Furthermore, NF-\u03baB has strongly related to\ninflammatory processes in musculoskeletal injury and acne vulgaris via\nactivated Toll-like receptor17<\/sup>; infectious diseases32<\/sup> and\ninflammation causing the progression of cardiovascular damage by Doxorubicin\ninduction.33<\/sup>  <\/p>\n\n\n\n

It has been demonstrated that serum CysC is an early\nand reliable biomarker of chronic kidney disease (CKD). This is especially\nuseful for patients for whom elevated creatinine is not a suitable marker or\nfor whom more sophisticated glomerular filtration rate (GFR) measurement\ntechniques are not feasible.34<\/sup> <\/p>\n\n\n\n

The renin-angiotensin system (RAS) pathway produces\nthe inflammatory hormone ACE2, which is secreted by excess adipose tissue in\nobesity. Insulin resistance and obesity are closely linked to RAS activity.\nFurthermore, RAS function is modulated by oxidative stress, inflammatory\nresponses, and mitochondrial dysfunction. When RAS function is compromised, the\ndetrimental processes stated above cause widespread dysfunction in the majority\nof tissues.35,36<\/sup> <\/p>\n\n\n\n

The purpose of this study is to find out the extent to which propolis affects the following parameters: body weight (BW), NF-\u03baB, CysC, Rohrer Index (RI), and ACE2 levels in Wistar rats (Ratus norvegicus) fed a high-fat diet (HFD)<\/p>\n\n\n\n

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

Animal experiment<\/strong><\/p>\n\n\n\n

This type of research is an experimental study that\nuses a control group and a post-test design. A total of thirty rats were split\ninto five groups at random, with the same number (n=6) in each group. The\nexperimental animal groups were divided into three groups: group I received a\nnormal diet (ND-0) for two weeks, group II received a high-fat diet (HFD-8) for\neight weeks, and group III served as the control. were given a normal diet for\neight weeks (ND-8), group IV received a high-fat diet for sixteen weeks\n(HFD-16), and group V received a normal diet for sixteen weeks (ND-16). <\/p>\n\n\n\n

All experimental animals have free access to food and\ndrink (ad libitum). Weight measurements were carried out every week in order to\nknow the increase in body weight of each rat. In each group, blood samples were\ntaken by intravenous to determine NF-\u03baB , CysC and ACE2  levels. <\/p>\n\n\n\n

Obese rats<\/strong><\/p>\n\n\n\n

Male Wistar strain white rats (Rattus norvegicus) that have been fed a high-fat diet (HFD) are referred to as obese rats. The Lee’s index and the Rohrer’s index were used to calculate the obesity of rats. If the Rohrer index is more than 30 and the Lee index is more than 300, mice are considered obese.37<\/sup> A high-fat diet, defined as one that contains the following macronutrient composition: 4.1% ash\/minerals, 21.4% fat, 50% carbohydrates, 3.5% fibre, and 7.5% protein, has been shown to induce weight gain and\/or obesity.36,38<\/sup><\/p>\n\n\n\n

Propolis Treatment <\/strong><\/p>\n\n\n\n

The propolis is part of Trigona Honey, obtained from\nbeekeeping in the Masamba subdistrict, South Sulawesi, Indonesia, and then\nthrough honey processing. In this place, the process is through settling,\nfiltering, and then it is obtained into Trigona honey in Medicinal Plants Laboratory of Hasanuddin\nUniversity Research Center, Indonesia.18,19 <\/sup>The\ndose of Propolis according to the previous study is 0.27 ml.18<\/sup> The dose of\nPropolis in this study is 0.27 ml per oral every day for 8 weeks for Group\nHFD-8 and 16 weeks for Group HFD-16. The dose of Propolis according to the\nprevious study is 0.27 ml. The dose of Propolis in this study is 0.27 ml per\noral every day for 8 weeks for Group HFD-8 and for 16 weeks for Group HFD-16. <\/p>\n\n\n\n

Examination of NF-\u03baB, CysC and ACE2 levels using the ELISA.<\/strong><\/p>\n\n\n\n

Using a 19\u201321 gauge tail intravenous needle, 0.5 ml of\nblood was drawn. The blood was then placed in a sample tube, and the serum was\nseparated using a 500x rpm centrifuge.<\/p>\n\n\n\n

Using the Enzyme Linked-Immunosorbent Assay (ELISA)\nTechnique, the levels of CysC, ACE2, and NF-\u03baB protein were examined. Before\nuse, the serum from the intravenous rat samples was taken out of the -80o<\/sup>C\nfreezer and placed on ice. To ensure that the ELISA results were valid, each\nsample was duplicated. The first step involved filling each well with 100 \u00b5L of\nAssay Diluent that contained protein buffer. Next, each well received 100 \u00b5L of\nStandard solution, which contained diluted samples from rat serum or\nrecombinant rat NF-\u03baB targets from the established kit. <\/p>\n\n\n\n

Next, it was incubated at room temperature for two\nhours. After filling each well with the liquid, rinse with sterile PBS. We did\nthis washing procedure four times in a row. Each well was then filled with 200\n\u00b5L of conjugate liquid containing streptavidin HRP, covered with a plastic\ncover, and allowed to incubate for two hours at room temperature. The liquid\nwas drawn in, and four more times, sterile PBS was used for washing. The\nfollowing procedure involved adding 200 \u00b5L of TMB-containing Substrate Solution\nto each well, which was then read using an ELISA Reader 270 (Biomerieux,\nFrance).11<\/sup><\/p>\n\n\n\n

Data analysis<\/strong><\/p>\n\n\n\n

A significance level of \u2264 0.001 was applied to all\ndata analyses performed using SPSS version 25.0. Figures, tables, and\nnarratives will be utilized for presenting the results of the analysis.<\/p>\n\n\n\n

To assess differences in BW, LI, RI, NF-\u03baB, CysC and ACE2 levels between groups given Propolis, HFD and ND, a one-way ANOVA test was used. To determine the correlation between duration of Propolis administration and BW, LI, RI, NF-\u03baB, CysC,and ACE2, the Pearson correlation test is used. The correlation between the Propolis group and BW, LI, RI, NF-\u03baB, CysC, and ACE2 was determined using the same test.<\/p>\n\n\n\n

Result<\/strong><\/p>\n\n\n\n

Effect of Propolis on increasing BW on HFD<\/strong><\/p>\n\n\n\n

Table 1 shows the effect of giving Propolis for both 8 weeks and 16 weeks on BW in Wistar rats (Rattus Norvegicus) model with HFD compared to ND. At the beginning of the study, weight was measured (week 0) and then measurements were carried out at week 8 (week 8) and week 16 (week 16).<\/p>\n\n\n\n

The initial\nmean weight in the ND group was 197.83 grams and increased to 202.00 grams at\nweek 8 and 208.67 grams at week 16. There was no significant increase in weight\nin the ND group between weeks 0 and 8 or 16 (p >0.001).<\/p>\n\n\n\n

On the other hand, there was a noteworthy increase in body weight (p<0.001) in the HFD group from weeks 0\u20138. The initial mean weight in the HFD group was 198.50 grams, then increased to 254.83 grams at week 8 and 334.83 grams at week 16 (Table 1).<\/p>\n\n\n\n

In the HFD group\nwith 8 weeks of Propolis administration, the initial mean BW was 197.33 grams\nand 214.33 grams at week 8. At week eight, there was not a significant increase\n(p >0.001) in BW between the pre-and post-8 weeks of propolis administration\n(HFD-8). The average body weight (BW) of the HFD-8 group at week 16 was 269.50\ngrams, and the BW of the HFD group increased significantly (p<0.001) between\nweeks 0 and 16 and between weeks 8 and 16 after receiving 8 weeks of propolis\n(HFD-8).<\/p>\n\n\n\n

Furthermore, there was not a significant increase in body weight (197.67 grams vs. 223.83 grams) between weeks 0 and 8 in the HFD-16 group that received propolis. Between week 0 and week 16, the mean body weight (BW) of the HFD-16 group increased significantly (p<0.001), from 197.67 grams to 223.83 grams. But in the HFD-16 group, there was not a significant increase in mean BW between weeks 8 and 16 (214.67 grams vs. 223.83 grams) (p>0.001). (Table 1)<\/p>\n\n\n\n

Table 1: Effect of Propolis on BW in HFD<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

BW (gram)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

mean \u00b1 SD<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

197.83 \u00b1 2.31 vs 202.0 \u00b1 3.74<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

197.83 \u00b1 2.31 vs 208.67 \u00b1 6.83<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

202.00 \u00b1 3.74 vs 208.67 \u00b1 6.83<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

198.50 \u00b1 3.14 vs 254.83 \u00b1 28.18<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

198.50 \u00b1 3.14 vs 334.83 \u00b1 11.94<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

254.83 \u00b1 8.18 vs 334.83 \u00b1 11.94<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

197.33 \u00b1 1.86 vs 214.33 \u00b1 7.73<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

197.33 \u00b1 1.86 vs 269.50 \u00b1 9.33<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

214.33 \u00b1 7.73 vs 269.50 \u00b1 9.33<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

197.67 \u00b1 3.88 vs 214.67 \u00b1 7.60<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

197.67 \u00b1 3.88 vs 223.83 \u00b1 11.01<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

214.67 \u00b1 7.60 vs 223.83 \u00b1 11.01<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

The pattern of BW increase following HFD, HFD + Propolis for 8 weeks (HFD-8) and HFD + Propolis for 16 weeks (HFD-16) is shown in Figure 1 starting from the study’s beginning (week 0), week 8, and week 16. The HFD group’s weight increased significantly between weeks eight and sixteen. The ND group’s weight did not significantly increase between weeks eight and sixteen. Meanwhile, an increase in weight was found in the HFD-8 group that was in line with the ND group. and HFD-16 at week 8, but by week 16 there had been a significant increase in weight. However, the increase in weight at week 16 was lower than with HFD. In contrast, the HFD-16 group shown an increase that was almost in line with the ND group both at week 8 and week 16. Between the beginning of the study and weeks eight and sixteen, there was not a significant increase in the ND group.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Effect of Propolis on Body Weight (BW) in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 )<\/strong><\/p>\n

<\/p>\n

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

Table 2 shows the effect of giving Propolis for both 8 weeks and 16 weeks on the LI in Wistar rats (Rattus Norvegicus) model with HFD compared to ND. LI was measured in week 0 of the study, and further measurements were carried out in weeks 8 and 16 of the study.<\/p>\n\n\n\n

In the ND\ngroup, the mean LI started at 222.00 and increased to 234.00 at week 8 and 250.00\nat week 16. There was no statistically significant increase in LI in the ND\ngroup between weeks 0 and 8 or 16 (p>0.001).<\/p>\n\n\n\n

In contrast, the HFD group shown a significant increase in LI between weeks 0, 8 and\/or week 16 (p<0.001). The initial mean LI in the HFD group was 220.00, then increased to 335.00 at week 8 and 375.00 at week 16 (Table 2).<\/p>\n\n\n\n

The initial\nmean LI in the HFD group receiving 8 weeks of Propolis was 222.00, and at week\n8, it was 258.00. At week eight, there was not a significant increase in LI\n(HFD-8) between pre- and post-8 weeks of propolis (p>0.001). At week 16, the\nHFD-8 group’s average LI was 310.00. The LI in the HFD group significantly\nincreased (p<0.001) between weeks 0 and 16 and between weeks 8 and 16\nfollowing the administration of 8 weeks of propolis (HFD-8).<\/p>\n\n\n\n

Furthermore, there\nwas not a significant increase in LI between weeks 0 and 8 in the HFD-16 group\nthat received propolis administration for 16 weeks (221.00 vs 257.00). Between\nweek 0 and week 16, the HFD-16 group’s mean LI significantly increased (221.00\nvs. 272.00) (p<0.001). Nonetheless, the HFD-16 group’s mean LI did not see\nan increase significantly between weeks 8 and 16 (257.00 vs. 272.00)\n(p>0.001). (Table 2<\/strong>)<\/p>\n\n\n\n

Table 2: Effect of Propolis on Lee Index (LI) in HFD <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

Lee Index<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

mean \u00b1 SE<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

222.00 \u00b1 12.00 vs 234.00 \u00b1 13.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

222.00\u00b1 12.00 vs 250.00 \u00b1 19.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

234.00 \u00b1 13.00 vs 250.00 \u00b1 19.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

220.00 \u00b1 21.00 vs 335.00\u00b1 24.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

220.00 \u00b1 21.00 vs 375.00\u00b1 13.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

335.00\u00b1 24.00 vs 375.00\u00b1 13.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

222.00\u00b1 15.00 vs 258.00\u00b1 27.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

222.00\u00b1 15.00 vs 310.00\u00b1 14.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

258.00\u00b1 27.00 vs 310.00\u00b1 14.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

221.00\u00b1 17.00 vs 257.00\u00b1 13.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

221.00\u00b1 17.00 vs 272.00\u00b1 15.00<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

257.00\u00b1 13.00 vs 272.00\u00b1 15.00<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

Figure 2 shows the pattern of increasing LI after administering HFD, HFD + Propolis for 8 weeks (HFD-8), and HFD + Propolis for 16 weeks (HFD-16) beginning at the beginning of the study (week 0), week 8, and week 16. In the HFD group, LI increased significantly between weeks eight and sixteen. From week 8 to week 16, the ND group did not show a statistically significant increase in LI. Meanwhile, in the HFD-8 group, an increase in LI was seen which was in line with the ND group. and HFD-16 at week 8, but then the increase in LI was quite sharp at week 16. However, the increase in LI at week 16 was lower than with HFD. In contrast, the HFD-16 group shown an increase that was almost in line with the ND group both at week 8 and week 16. In the ND group there was no significant increase seen from the start of the study until week 8 and week 16. Overall, the pattern of LI increase in line with the increase in BW based on the length of administration of Propolis.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Effect of Propolis on the Lee Index (LI) in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 )<\/strong><\/p>\n

<\/p>\n

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

Table 3 shows the effect of giving Propolis for both 8 weeks and 16 weeks on the RI in the Wistar rat (Rattus Norvegicus) model with a HFD compared to a ND. RI was measured in week 0 of the experiment, and additional measurements were performed in weeks 8 and 16 of the study. The initial mean RI in the ND group was 27.340 and increased to 29.28 at week 8 and 30.55 at week 16. In the ND group there was no significant increase in RI between week 0, week 8 and\/or week 16 (p>0.001).<\/p>\n\n\n\n

RI increased significantly (p<0.001) in the HFD group between weeks 0\u20138 and\/or 16 in contrast. In the HFD group, the mean RI started at 27.25 and was up to 51.58 at week 8 and 62.87 at week 16 (Table 3).<\/p>\n\n\n\n

The initial\nmean RI in the HFD group receiving 8 weeks of Propolis administration was 27.34,\nand at week 8, it was 30.29. At week eight (p>0.001), there was not a\nsignificant increase in RI between the pre- and post-8 weeks of propolis administration\n(HFD-8). At week 16, the HFD-8 group’s average RI was 44.74, and after\nreceiving 8 weeks of propolis (HFD-8), the HFD group’s RI significantly\nincreased between week 0 and 16 and between week 8 and 16.<\/p>\n\n\n\n

Moreover, there was not a significant increase in RI between weeks 0 and 8 in the HFD-16 group that received propolis administration for 16 weeks (27.29 vs 30.33). Between week 0 and week 16, the mean RI in the HFD-16 group increased significantly (27.29 vs 32.82) (p<0.001). Nonetheless, the HFD-16 group’s mean RI was not found to increase significantly between week 8 and 16 (30.33 vs 32.82) (p>0.001). (Table 3)<\/p>\n\n\n\n

Table 3: Effect of Propolis on RI in HFD <\/strong> <\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

Rohrer Index<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

mean \u00b1 SE<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

27.34 \u00b1 1.82 vs 29.28 \u00b1 1.41<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

27.34 \u00b1 1.82 vs 30.55 \u00b1 1.33<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

29.28 \u00b1 1.41 vs 30.55 \u00b1 1.33<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

27.25 \u00b1 1.27 vs 51.58 \u00b1 2.20<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

27.25 \u00b1 1.27 vs 62.87 \u00b1 1.44<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

51.58 \u00b1 2.20 vs 62.87 \u00b1 1.44<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

27.34 \u00b1 1.59 vs 30.29 \u00b1 1.27<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

27.34 \u00b1 1.59 vs 44.74 \u00b1 1.38<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

30.29 \u00b1 1.27 vs 44.74 \u00b1 1.38<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

27.29 \u00b1 1.51 vs 30.33 \u00b1 0.85<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

27.29 \u00b1 1.51 vs 32.82 \u00b1 2.09<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

30.33 \u00b1 0.85 vs 32.82 \u00b1 2.09<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

Figure 3 demonstrates the pattern of increasing RI after receiving HFD, HFD + Propolis for 8 weeks (HFD-8), and HFD + Propolis for 16 weeks (HFD-16) following the start of the study (week 0), week 8, and week 16. In the HFD group, RI increased significantly between weeks eight and sixteen. From week 8 to week 16, the ND group failed to show a statistically significant increase in RI. Meanwhile, in the HFD-8 group, an increase in RI was seen which was in line with the ND group. and HFD-16 at week 8, but then the increase in RI was quite sharp at week 16. However, the increase in RI at week 16 was lower than with HFD. On the other hand, the HFD-16 group saw an increase that was almost in line with the ND group both at week 8 and week 16. In the ND group there was no significant increase seen from the start of the study until week 8 and week 16. Overall, the RI pattern increased in line with changes in the increase in BW and LI based on the duration of Propolis administration.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3: Effect of Propolis on the Rohrer Index (RI) in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 ).<\/strong><\/p>\n

<\/p>\n

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

Table 4 shows the effect of giving Propolis for both 8 weeks and 16 weeks on NF-\u03baB in the Wistar rat (Rattus Norvegicus) model with a HFD compared to a ND. At the beginning of the study NF-\u03baB was measured (week 0) and after that, measurements were taken at weeks eight (week 8) and sixteen (week 16).<\/p>\n\n\n\n

After starting at 3.65 ng\/ml, the mean\nNF-\u03baB in the ND group increased to 3.74 ng\/ml at week 8 and 3.77 at week 16.\nThere was no statistically significant increase in NF-\u03baB in the ND group from\nweek 0 to week 8 or week 16 (p>0.001).<\/p>\n\n\n\n

On the other hand, NF-\u03baB significantly\nincreased in the HFD group between weeks 0\u20138 and\/or week 16 (p<0.001).\nBefore increasing to 5,038 ng\/ml at week 8 and 6,136 ng\/ml at week 16, the HFD\ngroup’s mean NF-\u03baB was 3.68 ng\/ml (Table 4).<\/p>\n\n\n\n

The initial mean NF-\u03baB in the HFD group\nreceiving 8 weeks of Propolis administration was 3,698 ng\/ml, and by week 8, it\nhad increased to 3.78 ng\/ml. <\/p>\n\n\n\n

There was no significant increase in NF-\u03baB\nbetween before and after 8 weeks of propolis administration (HFD-8) at week 8\n(p>0.001). The mean NF-\u03baB in the HFD-8 group at week 16 was 4.37 ng\/ml and\nthere was a significant increase in NF-\u03baB in the HFD group after administering\n8 weeks of propolis (HFD-8) between week 0 and 16 and between week 8 and week\n16 (p<0.001).<\/p>\n\n\n\n

Additionally, there was not a significant increase in NF-\u03baB between week 0 and 8 in the HFD group that received propolis for 16 weeks (HFD-16) (3.70 ng\/ml vs 3.81 ng\/ml). Between week 0 and week 16, the mean NF-\u03baB in the HFD-16 group did not significantly increase (3.70 ng\/ml vs. 3.85 ng\/ml) (p>0.001). Similarly, in the HFD-16 group, there was no statistically significant increase in mean NF-\u03baB between week 8 and week 16 (3.81 ng\/ml vs. 3.85 ng\/ml) (p>0.001). (Table 4)<\/p>\n\n\n\n

Table 4: Effect of Propolis on NF-\u03baB in HFD <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

NF-kB (ng\/ml)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Mean \u00b1 SE<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

3.65\u00b1 0.12 vs 3.74 \u00b1 0.06<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

3.65 \u00b1 0.12 vs 3.77 \u00b1 0.06<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

3.74 \u00b1 0.06 vs 3.77 \u00b1 0.06<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

3.68 \u00b1 0.15 vs 5.038\u00b1 0.20<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

3.68 \u00b1 0.15 vs 6.13\u00b1 0.05<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

5.03\u00b1 0.20 vs 6.13 \u00b1 0.05<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

3.69 \u00b1 0.14 vs 3.78 \u00b1 0.09<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

3.69 \u00b1 0.14 vs 4.37 \u00b1 0.14<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

3.78 \u00b1 0.09 vs 4.37 \u00b1 0.14<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

3.70 \u00b1 0.12 vs 3.81 \u00b1 0.12<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

3.70 \u00b1 0.12 vs 3.85 \u00b1 0.08<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

3.81 \u00b1 0.12 vs 3.85 \u00b1 0.08<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

Figure 4 demonstrates the pattern of increase in NF-\u03baB following HFD, HFD + Propolis for 8 weeks (HFD-8), and HFD + Propolis for 16 weeks (HFD-16) after the study’s start (week 0), week 8, and week 16. From week 8 to week 16, there was a significant increase in NF-\u03baB in the HFD group. From week 8 to week 16, there was not a significant increase in NF-\u03baB in the ND group.<\/p>\n\n\n\n

In\nthe meantime, NF-\u03baB increased in the HFD-8 group in line with the ND group. and\nHFD-16 at week 8, but at week 16, there was a seen increase in NF-\u03baB. In\ncontrast to the HFD group, the increase in NF-\u03baB at week 16 was, nevertheless,\nsmaller. On the other hand, at week 8 and week 16, the HFD-16 group saw an\nincrease that was similar to the ND group. <\/p>\n\n\n\n

In the ND group there was no significant increase seen from the start of the study until week 8 and week 16. Overall the pattern of increase in NF-\u03baB in line with changes in the increase in BW, LI and RI based on the duration of Propolis administration.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 4: Effect of Propolis on the NF-\u03baB in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 ).<\/strong><\/p>\n

<\/p>\n

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

Effect of Propolis on increasing CysC on HFD<\/strong><\/p>\n\n\n\n

Table 5 shows the effect of giving Propolis for both 8 weeks and 16 weeks on serum CysC levels in Wistar rats (Rattus Norvegicus) model with HFD compared to ND. At the start of the study CysC was measured (week 0) and then measurements were carried out at week 8 (week 8) and week 16 (week 16).<\/p>\n\n\n\n

In the ND group, the mean CysC started at 1.04 ng\/ml and went up to 1.06 ng\/ml at week 8 and 1.10 at week 16. There was not a significant increase in CysC in the ND group from week 0 to week 8 or week 16 (p>0.001). On the other hand, there was a noteworthy increase in CysC in the HFD group during weeks 0\u20138 and\/or 16 (p<0.001). In the HFD group, the mean CysC started at 1.04 ng\/ml and went up to 1.35 ng\/ml at week 8 and 1.90 ng\/ml at week 16 (Table 5).<\/p>\n\n\n\n

The\nmean initial CysC in the HFD group receiving 8 weeks of Propolis administration\nwas 1.04 ng\/ml, and by week 8, it had increased to 1.02 ng\/ml. At week eight,\nthere was not a significant increase in CysC between pre- and post-8 weeks of\npropolis administration (HFD-8) (p>0.001). At week 16, the mean CysC in the\nHFD-8 group was 1.47 ng\/ml. CysC in the HFD group increased significantly\n(p<0.001) after 8 weeks of propolis treatment (HFD-8) both between weeks 0\nand 16.<\/p>\n\n\n\n

Furthermore, in the HFD group given propolis for 16 weeks (HFD-16) there was no significant increase in CysC between week 0 and week 8 (1.04 ng\/ml vs 1.08 ng\/ml). There was no significant increase in mean CysC in the HFD-16 group between week 0 and week 16 (1.04 ng\/ml vs 1.12 ng\/ml) (p>0.001). Likewise, there was no significant increase in mean CysC between week 8 and week 16 in the HFD-16 group (1.08 ng\/ml vs 1.12 ng\/ml) (p>0.001). (Table 5)<\/p>\n\n\n\n

Table 5: Effect of Propolis on serum CysC level in HFD <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

Serum Cystatin C level  (ng\/ml)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

mean \u00b1 SE<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

1.042 \u00b1 0.02 vs 1.06 \u00b1 0.03<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.02 vs 1.10 \u00b1 0.02<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

1.06 \u00b1 0.03 vs 1.10 \u00b1 0.02<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.02 vs 1.35 \u00b1 0.08<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.02 vs 1.90 \u00b1 0.10<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

1.35 \u00b1 0.08 vs 1.90 \u00b1 0.10<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.03 vs 1.08 \u00b1 0.03<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.03 vs 1.47 \u00b1 0.16<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

1.08 \u00b1 0.03vs 1.47 \u00b1 0.16<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.02 vs 1.08 \u00b1 1.128<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.04 \u00b1 0.02 vs 1.12 \u00b1 0.06<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

1.08 \u00b1 1.12 vs 1.12 \u00b1 0.06<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

Figure 5 demonstrates the pattern of increasing CysC following HFD, HFD + Propolis for 8 weeks (HFD-8) and HFD + Propolis for 16 weeks (HFD-16) after the study’s start (week 0), week 8, and week 16. From week 8 to week 16, there was a significant increase in CysC in the HFD group. From week 8 to week 16, the ND group failed to show a statistically significant increase in CysC. Additionally, there was a gradual increase in CysC in the HFD-8 group. with the ND and HFD-16 groups at week 8, but by week 16, there had been an apparent increase in CysC. In contrast to the HFD group, the increase in CysC at week 16 was, nevertheless, smaller.<\/p>\n\n\n\n

On the other hand, at week 8 and week 16,\nthe HFD-16 group saw an increase that was nearly comparable to the ND group.\nThere was not a significant increase in the ND group from the beginning of the\nstudy until weeks eight and sixteen.<\/p>\n\n\n\n

Overall the pattern of increase in CysC in\nline with changes in the increase in BW, LI, RI and NF-\u03baB based on the duration\nof Propolis administration. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 5: Effect of Propolis on the CysC in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 )<\/strong><\/p>\n

<\/p>\n

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

Effect of Propolis on increasing ACE2 on HFD<\/strong><\/p>\n\n\n\n

Table 6 shows the effect of administering Propolis for both 8 weeks and 16 weeks on plasma levels of ACE2 in Wistar rats (Rattus Norvegicus) model with HFD compared to normal diet ND. At the start of the study ACE2 was measured (week 0) and then measurements were carried out at week 8 and week 16.<\/p>\n\n\n\n

In\nthe ND group, the mean ACE2\nstarted at 1,863 ng\/ml and went up to 1.94 ng\/ml at week 8 and 2.03 at week 16.\nThere was not a significant increase in ACE2 in the ND group from week 0 to\nweek 8 or week 16 (p>0.001).<\/p>\n\n\n\n

However, ACE2 increased significantly (p<0.001) in the HFD group between weeks 0\u20138 and\/or week 16 as well. In the HFD group, the mean ACE2 started at 1.86 ng\/ml and went up to 3.70 ng\/ml at week 8 and 4.91 ng\/ml at week 16 (Table 6).<\/p>\n\n\n\n

The initial mean ACE2 in the HFD group\nreceiving 8 weeks of Propolis was 1.86 ng\/ml, and by week 8, it had increased\nto 2.08 ng\/ml. At week eight, there was not a significant increase in ACE2\nbetween pre- and post-8 propolis (HFD-8) administration. (p>0.001). At week\n16, the average ACE2 in the HFD-8 group was 3.52 ng\/ml. The ACE2 in the HFD\ngroup increased significantly (p<0.001) between week 0 and 16 and between\nweek 8 and 16 following 8 weeks of propolis administration (HFD-8).<\/p>\n\n\n\n

Additionally, there was not a significant increase in ACE2 between weeks 0 and 8 in the HFD-16 group that received propolis (1.87 ng\/ml vs 2.06 ng\/ml). Between week 0 and week 16, the mean ACE2 in the HFD-16 group did not significantly increase (1.87 ng\/ml vs 2.11 ng\/ml) (p>0.001). In the HFD-16 group, there was also not a significant increase in mean ACE2 between weeks 8 and 16 (2.06 ng\/ml vs. 2.11 ng\/ml) (p>0.001). (Table 6)<\/p>\n\n\n\n

Table 6: Effect of Propolis on plasma ACE2 level in High Fat Diet HFD  <\/strong> <\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

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

\n

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

\n

Plasma ACE2 (ng\/ml)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

mean \u00b1 SE<\/strong><\/p>\n<\/td>\n

\n

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

\n

Normal Diet<\/p>\n<\/td>\n

\n

Week 0 vs 8<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.04 vs 1.94 \u00b1 0.08<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0 vs 16<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.04 vs 2.03 \u00b1 0.12<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

1.94 \u00b1 0.08 vs 2.03 \u00b1 0.12<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.04 vs 3.70 \u00b1 0.31<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.04 vs 4.91 \u00b1 0.05<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

3.70 \u00b1 0.31 vs 4.91 \u00b1 0.05<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(8 weeks only)<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.07 vs 2.08 \u00b1 0.12<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.86 \u00b1 0.07 vs 3.52 \u00b1 0.08<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

2.08 \u00b1 0.12 vs 3.52 \u00b1 0.08<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

HFD + Propolis
(16 weeks)<\/p>\n<\/td>\n

\n

Week 0  vs 8<\/p>\n<\/td>\n

\n

1.87 \u00b1 0.03 vs 2.06 \u00b1 1.13<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 0  vs 16<\/p>\n<\/td>\n

\n

1.87 \u00b1 0.03 vs 2.11 \u00b1 0.08<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Week 8 vs 16<\/p>\n<\/td>\n

\n

2.06 \u00b1 1.13 vs 2.11 \u00b1 0.08<\/p>\n<\/td>\n

\n

>0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p value <0.001 is significant different<\/p>\n\n\n

Following HFD, HFD + Propolis for 8 weeks (HFD-8) and HFD + Propolis for 16 weeks (HFD-16), Figure 6 demonstrates the pattern of increase in ACE2 starting from the beginning of the study (week 0), week 8 (week 8), and week 16 after giving HFD. From week 8 to week 16, there was a significant increase in ACE2 in the HFD group. There was not a significant increase in ACE2 in the ND group between weeks 8 and 16. In the meantime, the HFD-8 group’s ACE2 increased in a pattern in line with that of the ND group. and HFD-16 at week 8, but at week 16, there was a noticeable increase in ACE2.<\/p>\n\n\n\n

In\ncontrast to the HFD group, there was a less significant rise in ACE2 at week\n16. However, at weeks eight and sixteen, the HFD-16 group saw an increase that\nwas closely comparable to that of the ND group. In the ND group there was no\nsignificant increase seen from the start of the study until week 8 and week 16.\n<\/p>\n\n\n\n

Overall\nthe pattern of increase in ACE2 in line with changes in increasing BB, LI, RI, NF-\u03baB,\nand CysC based on the duration of Propolis administration.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 6: Effect of Propolis on the ACE2 in the ND, HFD groups, Propolis Administration for 8 weeks on HFD+Propolis (HFD-8) and Propolis Administration for 16 weeks on HFD+Propolis (HFD-16 )<\/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

Overweight and obesity are thought to be the cause of\n2.6 million deaths annually, according to WHO reports.1<\/sup> Previous\nstudy revealed that the relationship between obesity and renal failure through\nseveral pathways still unclear. <\/p>\n\n\n\n

From a biochemical perspective, obesity results from\nexcess triacylglycerol in fat tissue due to daily energy intake exceeding daily\nenergy expenditure. Obesity is associated with a significant increase in the\nmorbidity of chronic diseases, including depression, type II diabetes,\ncardiovascular disease, and immobility. Childhood obesity increases the risk of\ndeveloping chronic kidney disease (CKD) in adulthood and causes the same\nconditions to manifest earlier than usual.39<\/sup><\/p>\n\n\n\n

Several critical physiological responses, including\napoptosis, cell adhesion, proliferation, differentiation, and inflammation, are\nregulated by the NF-\u03baB family of transcription factors.11,12,29,33<\/sup>  The NF-\u03baB pathway relates to the metabolic and\ninflammatory responses. Being a major contributor to inflammation, the NF-\u03baB\npathway can be used as a starting point to find out more about metabolic\ndiseases like obesity caused by a high-fat diet.40<\/sup> \n<\/p>\n\n\n\n

Previous studies have demonstrated that a high-fat\ndiet (HFD) increases the activation of NF-\u03baB associated with increased levels\nof NADPH oxidase components. Additionally, HFD can cause oxidative stress in\nprostate tissue by involving NADPH oxidase activity and NF-\u03baB, which may result\nin intraprostatic inflammation and be a potential cause of prostate diseases\nsuch as BPH and prostate cancer.41<\/sup><\/p>\n\n\n\n

According to our study, administering Propolis during\na high-fat diet can effectively reduce the increase in NF-\u03baB levels. According\nto current studies, nutritional overload and metabolic stress cause the fat\ncell transcriptome to be reprogrammed toward inflammation through NF-\u03baB\nsignaling. According to certain studies, inhibiting NF-\u03baB signaling could\nassist with the metabolism of inflammation in adipose tissue associated with\nobesity.42<\/sup><\/p>\n\n\n\n

An essential protein identified as CysC is filtered by\nthe glomerulus after being non-glycosylated, and it is used as an indicator to\nassess kidney function. The information demonstrates a possible genetic\nconnection between non-alcoholic fatty liver disease in children and chronic\nkidney diseases. <\/p>\n\n\n\n

Adult studies indicate a positive relationship between\nCysC levels and BMI. Based on some studies, elevated CysC levels in obese\nchildren may serve as an early prognostic marker of vascular risk.43<\/sup>\n<\/p>\n\n\n\n

According to\nthe study’s findings, administering propolis can reduce an increase in Cys C in\nanimal models of high-fat diets (HFD), which indicates that propolis\nadministration can reduce the risk of obesity-related chronic kidney disease\n(CKD).<\/p>\n\n\n\n

It has been demonstrated that serum CysC is an early\nand reliable biomarker of chronic kidney disease (CKD). This is especially\nuseful for patients for whom creatinine is not a suitable marker or for whom\nmore complex techniques for determining glomerular filtration rate (GFR) are\nnot practicable.34<\/sup>  <\/p>\n\n\n\n

Through ectodomain shedding, the membrane-bound\nectoenzyme ACE2 is released into the bloodstream. The renin-angiotensin\nsystem’s positive or negative feedback is thought to be responsible for either\nectodomain shedding caused on by medication administration or disease, genetic\nfactors, or differential gene expression. It is difficult to establish the\nrelative contributions of each tissue to the blood’s release of ACE2, as\ncirculating proteins originate from nearly every part of the body.44<\/sup> <\/p>\n\n\n\n

According to the study’s findings, propolis\nadministration can stifle the rise in plasma ACE2 in animal models of high-fat\ndiets (HFD), which means that propolis administration can be utilized to\nprevent the decline in kidney function that results from an HFD in obesity.<\/p>\n\n\n\n

Angiotensin 2 (AT2), a hormone with inflammatory\ncharacteristics that is generated in the renin-angiotensin system (RAS)\npathway, is secreted by excess adipose tissue in obesity. Insulin resistance\nand obesity are closely linked to RAS activity. Furthermore, RAS function is\nmodulated by oxidative stress, inflammatory responses, and mitochondrial\ndysfunction. Through the detrimental mechanisms outlined above, a disruption in\nRAS function results in widespread dysfunction in the majority of tissues.35<\/sup>\nRenin converts\nangiotensinogen to angiotensin I (ATI) at the cellular level. To synthesize\nangiotensin 2 (AT2), the angiotensin converting enzyme (ACE) cleaves AT1. After\nAT2 interacts with type I G protein-coupled receptors on the cell surface, AT1R\ninitiates a series of conditions that include insulin resistance, oxidative\nstress, vasoconstriction and inflammation.35,45<\/sup> <\/p>\n\n\n\n

In a conclusion of this study, giving propolis for 16\nweeks can prevent obesity, suppress the inflammatory process, prevent the risk\nof CKD and prevent damage to kidney function in obesity due to HFD. This shows\nthat giving Propolis can be used as a supplement to suppress increases in BW,\nNF-\u03baB, CysC and ACE2 in obesity.<\/p>\n\n\n\n

The limitation of this study is that it only looks at the upstream molecular mechanisms of Propolis as an anti-obesity agent and does not yet explore in detail at the pathway of NF-\u03baB activity which is related to pro-inflammatory cytokines such as IL6 and TNF\u03b1. Other than that, no studies have been done to explore how propolis influences the dynamics of the process in terms of preventing glomerular damage and performing as an anti-obesity agent.   <\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Propolis administration can suppress the increase in BW, LI, RI, NF-\u03baB, CysC and ACE2 protein levels in the HFD group after administration of propolis for 8 weeks and 16 weeks. Furthermore, a positive correlation was found between BW, LI, RI, NF-\u03baB, Cy C and ACE2 protein levels in the HFD group after giving propolis for 8 weeks and 16 weeks compared to and normal diet in Wistar rats with HFD.<\/p>\n\n\n\n

Further study is needed to explore in the downstream\nmolecular mechanisms of Propolis as anti-obesity and anti-inflammatory and a\nmore detailed in the pathway of NF-\u03baB activity related to pro-inflammatory\ncytokines such as IL6 and TNF\u03b1 is needed.<\/p>\n\n\n\n

Also, further study is needed to explore on the dynamics of changes in BW, LI, RI, NF-\u03baB, CysC and ACE2 protein levels and the process as an anti-obesity and anti-inflammatory after Propolis treatment.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

Authors would like to thank Romi Usman, Mus Jubaru, Wani, and Markus of Molecular Biology and Immunology Laboratory for Infection Diseases, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia who helped in the search of journals.<\/p>\n\n\n\n

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

The authors declare no conflict of interest, financial or otherwise.<\/p>\n\n\n\n

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

No specific funding are available.<\/p>\n\n\n\n

Availability of Data and Materials<\/strong> <\/p>\n\n\n\n

The authors confirm that the data supporting the findings of this study are available within the article.<\/p>\n\n\n\n

Ethic\nApproval <\/strong><\/p>\n\n\n\n

The research was conducted at\nthe Laboratory of Molecular Microbiology and Immunology, Faculty of Medicine,\nUniversity of Hasanuddin Makassar. The research was obtaining approval for\nethical clearance from the health research ethics committee of the Faculty of\nMedicine UNHAS Makassar, Indonesia, No. 221\/UN4.6.4.5.31\/PP36\/2024; dated 27,\nMarch, 2024, according to Helsinki Declaration.<\/strong><\/p>\n\n\n\n

Authors Contributions<\/strong><\/p>\n\n\n\n

Muhammad Reza Primaguna (MRP), Haerani Rasyid (HR), Makbul Aman (MA), Syakib Bakri (SB), Hasyim Kasim (HK), Harun Iskandar (HI), Ressy Dwiyanti (RR), Ade Rifka Junita (ARJ), Ridwan Ridwan (RR), Rizki Amelia Noviyanthi (RAN), Nur Indah Purnamasari (NIP), Mochammad Hatta (MH) MRP, HR, MA, SB, RR and MH conceived and designed the study, conducted research, provided materials, and collected and organized data. MRP, HR, HK, HI, RR, RAN, NIP, and MH drafted the manuscript. MRP, HR, RD, RR, ARJ, RAN, NIP and MH analysed the data and interpreted data. MRP, HR, MA, RR, ARJ, RAN, NIP and MH wrote initial and final draft article, and provided logistic support. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.<\/p>\n\n\n\n

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