INTRODUCTION:

High-intensity physical exercise such as resistance training is an important component of an overall fitness regimen for athletes and recreationally active people^1–3. High-intensity physical exercise is good for increasing lean muscle mass, but Exercise Induced Muscle Damage (EIMD), Delayed Onset Muscle Soreness (DOMS), can limit performance after a training session^4–8.

Several studies have reported that muscle pain reaches its peak 24 hours after exercise⁹. In connection with this phenomenon, currently, around 30 million people worldwide who experience DOMS are usually treated with non-steroidal anti-inflammatory drugs (NSAIDs)^10,11. Giving NSAIDs after exercise has the effect of inhibiting hypertrophy and muscle strength. resulting in giving NSAIDs will actually negate the results of the exercise performed¹².

High-intensity physical exercise will increase Nuclear Factor-kappa Betta (NF-kB) signaling so that it will trigger inflammation¹³. Meanwhile, muscle pain is caused by increased levels of pro-inflammatory cytokines, namely Tumor Necrosis Factor Alpha (TNF-a) in the blood in response to muscle damage¹⁴. TNF-α at the correct levels will provide protection and healing, but at excessive levels, it will cause tissue damage^1,15. Other alternative solutions need to be sought to reduce complaints of muscle pain, but still not interfere with the response of muscle growth after exercise. One of the natural ingredients contained in turmeric is curcumin. Curcumin is known for its active compounds that have anti-inflammatory activity^16–18. Curcumin is able to inhibit inflammation by modulating NF-kB signals and blocking TNF-α signals by activating protein responses in muscles¹⁹. The anti-inflammatory activity of curcumin also inhibits the production of pro-inflammatory eicosanoids which include prostaglandins and leukotrienes^20,21. Curcumin has been widely used to increase endurance and VO2 max²². In addition, curcumin has been widely used in the medical world to accelerate wound healing^23,24. Until now, curcumin has never been reported to cause post-exercise side effects, but the effect of curcumin on reducing muscle pain is unknown by reducing TNF-α signals due to inflammation after high-intensity physical exercise in untrained people.

The purpose of this study was to analyze and prove the effect of curcumin on TNF-α levels, and pain intensity after high-intensity physical exercise.

MATERIAL AND METHODS:

Study Design:

This experimental research uses pre and post control group design. Research subjects were selected using a random sampling technique, then the subjects were divided into 2 groups, namely group (K1) with placebo and group (K2) with curcumin.

Subjects:

A total of 20 healthy men participated in this study (subject characteristics are shown in table 1). The inclusion criteria in this study were men aged 20 to 30 years, with normal BMI, and not trained in sports. Exclusion criteria in this study were subjects under 20 years of age and abnormal blood pressure before exercise. The criteria for dropping out in this study were consuming coffee, consuming foods containing turmeric, consuming non-steroidal anti-inflammatory drugs (NSAIDs), and doing massage. research subjects received instructions about research procedures and signed a written consent willing to become research subjects.

Procedure:

1. In the beginning, we prepared administration such as ethical eligibility permits and permits for borrowing facilities and infrastructure

2. We screened respondents who were used as research subjects based on inclusion and exclusion criteria and filled out the form willing to become research subjects (Informed Consent) by research subjects.

3. Subjects were divided into two groups, namely the group receiving a placebo and the group receiving curcumin. Placebo was given in the form of empty capsules and curcumin was given at a dose of 400 mg.

4. On the first day, all subjects collected data on the characteristics of the research subjects, then did a warm-up, and then the subjects did physical exercises in the form of squad exercises and leg presses with an intensity of 80-90% of their maximum ability. Exercise is done 4 sets of each form of exercise and rest between sets of about 1 minute.

5. The second day, after 24 hours post-exercise, all subjects measured pain intensity and took pre-test blood samples to measure TNF-a levels, then administer interventions based on each group. Pain intensity was measured using a Visual analog scale (VAS).

6. On the third day, after 48 hours post-exercise, all subjects measured pain intensity and took post-test blood samples to measure TNF-a levels.

7. Blood samples were analyzed in the laboratory using the ELISA method with catalog numbers Human TNF-a ELISA kit E0082Hu.

CONSORT flowchart:

Figure 1. The CONSORT flowchart

Statistical analysis:

Statistical analysis in this study used the IBM SPSS version 27 application, a descriptive test was performed to obtain the mean, standard deviation and standard error. Furthermore, the normality test was carried out using the Shapiro-Wilk method, if the data were normally distributed the different test was carried out using the paired t-test, but if the data was not normally distributed, the difference was carried out using the Wilcoxon signed rank test.

Ethics:

This research protocol has been declared ethical in accordance with 7 (seven) WHO 2011 standards, namely 1) social value, 2) scientific value, 3) distribution of burdens and benefits, 4) risk, 5) seduction / exploitation, 6) confidentiality and privacy 7) Approval after explanation, which refers to the 2016 CIOMS guidelines. This is shown by the fulfillment of indicators for each standard. Declaration of ethics was approved by the Health Research Ethics Committee of the Faculty of Medicine, Universitas Airlangga with registration number (No.118/EC/KEPK/FKUA/2022).

RESULTS:

Data on the characteristics of the research subjects are shown in Table 1.

Table 1. Characteristics of research subjects

Data	Group	N	x̄±SD	Shapiro-Wilk	p-value
Age	K1	10	22.60±1.83	0.149	0.389
Age	K2	10	23.30±1.70	0.850	0.389
Height	K1	10	166.95±4.46	0.891	0.179
Height	K2	10	169.80±4.64	0.243	0.179
Weight	K1	10	63.55±9.11	0.823	0.938
Weight	K2	10	63.20±10.68	0.386	0.938
BMI	K1	10	23.13±4.20	0.046	0.173
BMI	K2	10	21.70±3.17	0.477	0.173
Body temperature	K1	10	36.56±0.26	0.184	0.619
Body temperature	K2	10	36.47±0.49	0.523	0.619
Systolic	K1	10	123.00±6.27	0.475	0.355
Systolic	K2	10	119.80±8.62	0.987	0.355
Diastolic	K1	10	75.30±6.66	0.100	0.385
Diastolic	K2	10	71.60±11.31	0.385	0.385
Pulse	K1	10	84.70±5.45	0.053	0.165
Pulse	K2	10	88.70±6.83	0.779	0.165

In the table above, only BMI K1 data is not normally distributed, so the Wilcoxon Signed Ranks Test is used for different tests. All data from the table above did not differ significantly in each group.

Curcumin reduces TNF-a levels:

Table 2. Normality Test Results for TNF-a Levels

Data	Group	Shapiro-Wilk
Data	Group	n	p-value
TNF-a levels (Pre-test)	K1	10	0.159
TNF-a levels (Pre-test)	K2	10	0.737
TNF-a levels (Post-test)	K1	10	0.060
TNF-a levels (Post-test)	K2	10	0.477

P>0.05 = Data is normally distributed

The results of the analysis of TNF-a levels between the pre-test and post-test in each group are presented in Figure 2.

Figure 2. Group (K2) which was given curcumin after high-intensity exercise was able to reduce TNF-a levels significantly (*p=0.016) compared to group (K1) which was given a placebo (p=089). Data presented as Mean ± Std Error. The P-value was obtained using a paired t-test to compare the pre-test and post-test of each group

Curcumin reduces pain intensity:

Table 3. Pain Intensity Normality Test Results

Data	Group	Shapiro-Wilk
Data	Group	n	p-value
Pain Intensity (Pre-test)	K1	10	0.478
Pain Intensity (Pre-test)	K2	10	0.051
Pain Intensity (Post-test)	K1	10	0.140
Pain Intensity (Post-test)	K2	10	0.426

P>0.05 = Data is normally distributed

The results of the analysis of pain intensity between the pre-test and post-test in each group are presented in Figure 3.

Figure 3. Group (K2) which was given curcumin after high-intensity physical exercise was able to reduce pain intensity significantly (*p=0.000) compared to group (K1) which was given a placebo (p=0.454). The data presented is in the form of mean, std error, and p-value

DISCUSSION:

This study was conducted to analyze the effect of curcumin on levels of TNF-a, and pain intensity after high-intensity physical exercise.

We observed that the placebo group did not significantly decrease TNF-a levels and pain intensity after high-intensity physical exercise, while the 400 mg curcumin group significantly reduced TNF-a levels, and pain intensity. Our research answer and confirm a literature study reported findings that curcumin has a positive effect on inflammatory responses²⁵. High-intensity physical exercise, especially with eccentric movements, will result in muscle damage and inflammatory response^26,27. Eccentric movements contribute to high mechanical stress and produce bone extracellular matrix fragments that are recognized by receptors expressed by innate immune cells²⁷. Cell activation mediated by this process stimulates NF-kB activation²⁸.

A theory reports that NF-kB plays a role in controlling inflammation, especially in the secretion of pro-inflammatory cytokines such as TNF-a and IL-6²⁷. In this regard, we believe that the main cause of muscle pain is due to an uncontrolled increase in pro-inflammatory cytokines such as TNF-a for several days after high-intensity physical exercise. In the case of exercise-induced muscle damage, a histological study showed that neutrophils enter the muscles and accumulate in the damaged area from 1 to 24 hours after exercise²⁹. In addition, muscle damage is characterized by ultrastructural disturbances of the muscles which increase the release of inflammatory cytokines by macrophages²⁷. Neutrophils and pro-inflammatory cytokines that interact with each other aim to control the pro-inflammatory response when muscle damage occurs³⁰. On the other hand, while pro-inflammatory cytokines increase, macrophages also release anti-inflammatory cytokines that contribute to muscle recovery and regeneration³¹.

We believe the role of NF-kB is the therapeutic goal of curcumin in inflammation because of the importance of NF-kB in the regulation and expression of TNF-a which is a cause of muscle pain. Our research findings are supported by an experimental study on the effect of curcumin on NF-kB expression in rats induced by drinking ethanol [8]. In that study, curcumin can significantly reduce NF-kB levels. In addition, a study reported that curcumin is able to attenuate osteoarthritis through the NF-kB pathway³². Curcumin is one of the natural ingredients that have anti-inflammatory activity^33,34. A recent literature study reported that curcumin works by suppressing the secretion of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, IL-17, and TNF-a^35,36. Research on the effect of curcumin on TNF-a levels after exercise is perhaps limited. However, on the other hand, we found a study that reported that there was no significant reduction in TNF-a levels given curcumin at a dose of 1500 mg/day for 28 days after aerobic exercise in trained men²⁰. We analyzed from this study that the ineffective effect of curcumin is probably due to aerobic exercise which is classified as moderate exercise intensity so it does not trigger post-exercise inflammation. In this regard, what distinguishes this research is that the subjects involved are people who are not trained and the exercises are carried out with high intensity. This is a strong foundation that physical exercise performed at high-intensity results in muscle damage and triggers an increase in pro-inflammatory cytokines such as TNF-a and IL-6 in the blood⁹. On the other hand, at the right levels, TNF-a will provide protection and healing, but at excessive levels, TNF-a will cause tissue damage and trigger muscle pain³⁷.

In summary, interesting new findings in this study report that curcumin given at a dose of 400 mg/day is able to reduce TNF-a and pain intensity after high-intensity physical exercise. Based on the laboratory tests we conducted, we believe the reduction in pain intensity occurred due to the anti-inflammatory effect of curcumin which is able to block TNF-a signals. The limitation of this study is that it did not test other inflammatory biomarkers such as IL-1a, IL-6, IL-18 and IL-10.

CONCLUSION:

Giving a dose of 400 mg of curcumin after high-intensity physical exercise can reduce TNF-a levels and pain intensity after high-intensity physical exercise. Because reduction in pain intensity after high-intensity exercise is necessary to support body function, we recommend the use of curcumin for individuals who actively exercise. For future studies, we suggest testing the effects of curcumin on other inflammatory biomarkers.

CONFLICT OF INTEREST:

The authors declare no conflict of interest

ACKNOWLEDGMENTS:

The author would like to thank BPPT and LPDP as funders/sponsors.

AUTHORS’ CONTRIBUTIONS

NA, NWK, LH, AK, MFH, DFP: conceptualization, methodology, writing. AZR, AA, APSW: Translate and statistical analysis. All authors agreed to submit this study to the current journal, gave final approval to the version to be published, and agreed to be accountable for all aspects of the work.

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Received on 05.11.2024 Revised on 11.03.2025

Accepted on 06.05.2025 Published on 01.10.2025

Available online from October 04, 2025

Research J. Pharmacy and Technology. 2025;18(10):4909-4914.

DOI: 10.52711/0974-360X.2025.00708

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.