QUANTITATIVE DETERMINATION OF FURANODIENES

The chemical composition of MyrLiq® comprises several furanodienes, including the bioactive compounds curzerene, furanoeudesma-1,3-diene and lindestrene (Figure 1). The presence of these three major furanodienes is typical of the genus, and these compounds are primarily responsible for the analgesic effects of myrrh extracts.

Figure 1. The major bioactive furanodienes of MyrLiq®

MyrLiq® extracts are analyzed by gas chromatography (GC) coupled to mass spectrometry (MS) for qualitative analysis of the compounds and by GC coupled to flame ionization detection (FID) for quantitative analysis. Figure 2 shows a typical GC-MS profile of MyrLiq.

Figure 2. GC-MS chromatogram of MyrLiq®

Table 1 shows the typical chemical composition of MyrLiq-PWD.

Table 1. Furanodiene content of MyrLiq®. Data are expressed as the relative area percentage and content (standard deviation).

Compound Furanodiene area percentage Content (g kg-1)
Curzerene 17.93 (0.20) 12.31 (0.05)
Furanoeudesma-1,3-diene 27.44 (0.17) 18.84 (0.02)
Lindestrene 9.08 (0.06) 6.23 (0.01)
Dihydrolinderalactone 1.91 (0.02) 1.31 (0.02)
Acetoxy-furanodiene (M.W. = 274) 0.87 (0.05) 0.59 (0.03)
Acetoxy-furanodiene (M.W. = 232) 1.85 (0.04) 1.27 (0.03)
TOTAL 59.07 (0.43) 40.56 (0.78)

GC-FID quantitative analyses revealed that the total percentage of identified furanodienes is approximately 60% of the total volatile fraction, whereas the total furanodiene content is >40 g kg-1 (SD = 0.78) (Table 1). These results are in agreement with the typical percentage and content of furanodienes in myrrh.

The precise quantification of furanodienes and their standardization in MyrLiq® allows the preparation and accurate dosage of products based on MyrLiq®. For instance, in a recent clinical study (see below) we tested two dosages of tablets containing either 200 or 400 mg of MyrLiq®, corresponding to 8.17 mg and 16.34 mg of total furanodienes, respectively.

ANALGESIC PROPERTIES OF MYRLIQ®: CLINICAL TRIALS

Female and male volunteers were selected based on different pain categories, including:

  • HEADACHE
  • FEVER-DEPENDENT PAIN
  • JOINT PAIN
  • MUSCLE ACHES
  • LOWER BACK PAIN
  • MENSTRUAL CRAMPS

The volunteers were asked to compare the effects of MyrLiq® with the drug they had been taking for the specific pain they were experiencing (DI = diclofenac; KE = ketoprofen; IB = ibuprofen; PA = paracetamol; TR = tramadol; KT = ketorolac). We asked the volunteers to score the effects of MyrLiq® on a scale between 0 and 10, with 0 indicating no effect and 10 indicating an effect comparable to that of the drug they had been using to treat the pain.

MyrLiq® was administered once a day at two dosages: 200 mg or 400 mg.

Table 2 presents the demographic and baseline characteristics of the volunteers.
(W = women; M = men)

Demographics Experimental Group, MyrLiq® Administration Placebo Group
Number of volunteers 184 184
Number of women (%) 95 (51.6) 95 (51.6)
Number of men (%) 89 (48.4) 89 (48.4)
Median age (range) 38 (19-61) 38 (19-63)
Age range:
18-35 21 (W), 9 (M) 21 (W), 9 (M)
36-45 27 (W), 26 (M) 27 (W), 26 (M)
46-60 29 (W), 30 (M) 29 (W), 30 (M)
over 60 18 (W), 24 (M) 18 (W), 24 (M)
MyrLiq®-PWD 200 mg 34 (W); 39 (M) 34 (W); 39 (M)
MyrLiq®-PWD 400 mg 61 (W); 50 (M) 61 (W); 50 (M)
Baseline level
Number for headaches (%)
Comparison with KE, IB, PA
33 (W), 17 (M) 33 (W), 17 (M)
Number for fever-dependent pain (%)
Comparison with PA
12 (W), 19 (M) 12 (W), 19 (M)
Number for joint pain (%)
Comparison with DI, KE
23 (W), 20 (M) 23 (W), 20 (M)
Number for muscle aches (%)
Comparison with DI, KE, PA
14 (W), 22 (M) 14 (W), 22 (M)
Number for lower back pain (%)
Comparison with DI, KE, TR, KT
3 (W), 11 (M) 3 (W), 11 (M)
Number for menstrual cramps (%)
Comparison with KE, IB
10 (W) 10 (W)
Number of tablets (days) 1 (20) 1 (20)
Volunteers not completing the study (%) 18 (9.9) 33 (18.2)
Women not completing the study (%) 11 (11.4) 23 (24.1)
Men not completing the study (%) 7 (8.3) 10 (11.8)

Overall, the scores assigned by the patients were explained by the administration of the placebo or MyrLiq® (see the results for individual diseases), whereas no significant differences related to sex and age were observed (P > 0.05 for each model).
We considered values ≥ 5 as a threshold score for the volunteers.

In general, the level of pain experienced by the volunteers was comparable to the second level of the World Health Organization analgesic ladder.

MyrLiq® significantly reduces HEADACHE pain in both men and women

Figure 3 Effects of MyrLiq® on headache reduction in male and female volunteers. The top boxplots show the effects of the treatments and placebo on the different age groups independent of the MyrLiq® concentration. The boxplots show the median, quartile, maximum and minimum score values, and the outliers are identified with open asterisks. The lower boxplots show the effects of the two concentrations of MyrLiq® (200 and 400 mg) with respect to the placebo (P) independent of age.

In both males and females, reduction in headache pain was obtained with the lowest concentration of MyrLiq® (200 mg), as shown by the median indicating values > 5 (e.g., for 200 mg Myrliq for both males and females the median value is 8).

MyrLiq® alleviates FEVER-DEPENDENT PAIN

Figure 4. Effects of MyrLiq® on fever-dependent pain reduction in male and female volunteers. The top boxplots show the effects of the treatments and placebo on different age groups independent of the MyrLiq® concentration. The lower boxplots show the effects of the two MyrLiq® concentrations (200 and 400 mg) compared with the placebo (P) independent of age. Pain caused by fever was already effectively reduced by 200 mg of MyrLiq® in both the male and female volunteers, with a marked effect in women (the only group able to reach a threshold > 5 at this dosage). MyrLiq® did not lower the fever (i.e., had no antipyretic activity). However, it did reduce the side effects of fever, including headache, general muscular pain and dizziness. When used at 400 mg, MyrLiq® significantly reduced fever-dependent pain in both males and females.

MyrLiq® significantly reduces JOINT PAIN

Figure 5. Effects of MyrLiq® on joint pain reduction in male and female volunteers. The top boxplots show the effects of the treatments and placebo on different age groups independent of the MyrLiq® concentration. The lower boxplots show the effects of the two MyrLiq® concentrations (200 and 400 mg) with respect to the placebo (P) independent of age. Notably, MyrLiq® was more effective for women than men when used at a dose of 200 mg. The latter group reported significant effects only at a dose 400 mg of MyrLiq®. However, when used at 400 mg, MyrLiq® always significantly reduced joint pain.

MyrLiq® used at 400 mg/day significantly reduces MUSCLE ACHES

Figure 6. Effects of MyrLiq® on the reduction of muscle aches in male and female volunteers. The top boxplots show the effects of the treatments and placebo on different age groups independent of the MyrLiq® concentration. The lower boxplots show the effects of the two MyrLiq® concentrations (200 and 400 mg) with respect to the placebo (P) independent of age. As found for joint pain reduction, even in the case of muscle aches MyrLiq® shows a significant analgesic activity when used at 400 mg/die.

LOW BACK PAIN is reduced by MyrLiq® at both 200 and 400 mg/die

Figure 7. Effects of MyrLiq® on lower back pain (LBP) reduction in male and female volunteers. The top boxplots show the effects of the treatments and placebo on different age groups independent of the MyrLiq® concentration. The lower boxplots show the effects of the two MyrLiq® doses (200 and 400 mg) with respect to the placebo (P) independent of age. A significant reduction of LBP was observed after administration of 200 mg and 400 mg of MyrLiq®.

MyrLiq® reduces pain from MENSTRUAL CRAMPS

Figura 6. Effects of MyrLiq® on the reduction of menstrual cramps in female volunteers. The top boxplot shows the effects of the treatments and placebo on different age groups independent of the MyrLiq® concentration. The lower boxplot shows the effects of the two MyrLiq® concentrations (200 and 400 mg) with respect to the placebo (P) independent of age. MyrLiq® reduced pain from menstrual cramps, with significant effects already observable at the 200-mg dose of MyrLiq®. However, the score was below the limit threshold (i.e., 5); therefore, the most significant effect on alleviation of menstrual cramps was found after administration of 400 mg MyrLiq®/die.

Summary of analgesic activity of MyrLiq®

MyrLiq® is a myrrh extract with the highest content of bioactive furanodienes on the market. The results of the clinical study indicate that MyrLiq® has analgesic activities against some of the most prevalent and distressing pain symptoms, particularly headaches, muscle aches, joint pain, lower back pain, fever-dependent pain and menstrual cramps. A direct comparison with some of the most frequently used drugs (e.g., diclofenac, ketoprofen, ibuprofen, paracetamol, tramadol and ketorolac) reveals that MyrLiq® has similar effects, although it requires a longer course of treatment (20 days). In male volunteers, the analgesic effects are particularly significant at a dose of 400 mg of MyrLiq®/day for almost all pathologies, whereas for female volunteers, lower back pain and fever-dependent pain were already significantly alleviated after treatment with 200 mg of MyrLiq®/day. No side effects were reported by any of the volunteers. Our results confirm the analgesic properties of MyrLiq® furanodienes and support their application as a natural remedy for a wide range of pathologies in which analgesic effects are required to alleviate pain and improve quality of life.

For further reading on the quantitative analysis of furanodienes and clinical studies refer to the publication:

Germano A., Occhipinti A., Barbero F., Maffei M.E. (2017)
A Pilot Study on Bioactive Constituents and Analgesic Effects of MyrLiq®, a Commiphora myrrha Extract with a High Furanodiene Content.
BioMed Research International, in press, Article ID 3804356 (read online)

MECHANISM OF ACTION AND EFFICACY OF MYRLIQ®

Studies conducted on myrrh furanodienes demonstrate that furaneudesma-1 ,3-diene and curzerene (the main furanodienes of MyrLiq®) have analgesic activity due to their interaction with opioid receptors of the central nervous system. Furthermore, some furanodienes show local-anesthetic properties due to the selective and reversible block of sodium channels. The myrrh extract inhibits the production of IL-6 and IL-8 in cells of human gingival fibroblasts; blocks proteins involved in the inflammatory process such as Cox; inhibits the formation of NO, ROS, TNF-α, PGE2, NF-kB and MAPK. Clinical studies indicate that the extract of myrrh also induces significant improvements of osteoarthritis.

Recently, an open label prospective study enrolling 50 community adults (55-75y) affected by joint pain and stiffness showed that a preparation containing MyrLiq®-PWD was effective and safe without any adverse side effects on general metabolism and other organic functions. Administration for 6 months induced a significant reduction in joint pain and stiffness in subjects with mild osteoarthritis (as for the conclusions that has been reported in other studies using chondroprotective or anti-inflammatory dietary supplements) and mitigated the difficulties to performing daily activities in subjects with knee pain and stiffness (Vianello, R. 2016. Efficacy and safety of DAIGO® Artiplus a chondroprotective agent in patients with joint pain and stiffness: a 6 months prospective study. Int. J. Exper. Clin. Res. 5: 5-8).

OTHER CLINICAL STUDIES WITH MYRLIQ®

MyrLiq® and UTI

A prospective non-randomized phase II clinical trial in order to evaluate the efficacy of a combination of Myrliq® with hibiscus extract and plant proteases in the prophylaxis of symptomatic episode in women affected by recurrent UTIs focusing on both the capability to reduce the number of symptomatic recurrences and the efficacy in improving quality of life. Fifty-five women were enrolled (mean age 49.3; range: 28-61). At the time of enrollment, the most common isolated pathogen was Escherichia coli (63.7%). The median number of UTI per 6 months was 5 (IQR 4-9). After 3 months from the beginning of the treatment, 43 out of 51 patients (84.3%) reported a clinical improvement in terms of quality of life form the baseline (p < 0.001), while 42 out of 51 patients (82.3%) reported a restore to pre-UTI situation. From a microbiological point of view, 40 patients (78.4%) showed sterile urine and 11 (20%) showed a transition from UTI to ABU (from Escherichia coli to Enterococcus faecalis). At the end of the second follow-up evaluation, 25 women did not report any acute episode of UTI (49%), 18 reported less than 2 episodes (35.3%), while 8 reported more than 2 episodes (15.7%). Overall, a statistically significant improvement in the quality of life was reported in almost 74.5% of patients and in 84% at first and second follow up visit, respectively.

For further reading on this clinical study refer to the publication:

Cai T., Tiscione D., Cocci A., Puglisi M., Cito G., Malossini G., Palmieri A. (2018)
Hibiscus extract, vegetable proteases and Commiphora myrrha are useful to prevent symptomatic UTI episode in patients affected by recurrent uncomplicated urinary tract infections.
Archivio Italiano di Urologia e Andrologia; 90, 3(read pdf)

MyrLiq® and Migraine

The objective of this pilot observational study was to assess the efficacy and safety of a new nutraceutical containing MyrLiq® (150 mg) along with Ginkgo biloba (150 mg), coenzyme Q10 (10 mg) and riboflavinin (2.4 mg) oral administration once per day for 3 months for the prophylaxis of migraine without aura. Headache diary was request to record the frequency of headache in days/month, the duration of attack in hours, the average intensity of attacks using visual analog scale (VAS) with the pole 0 (no pain) and 10 (unbearable) and adverse events. A small sample of 16 patients with migraine without aura was enrolled in the study; all patients were recruited from tertiary care outpatient clinic. Mean age 41 years (15–61 years), 87% women; mean years with migraine was 13.8 years (range 2–40 years); 37.5% reported a positive family history of headache; 75% of patients had never taken prophylactic therapy; and in 25% a previous prophylaxis was referred as ineffective. After treatment a significant reduction of the headache frequency and attack intensity 75 and 33.3% (p < 0.001) was observed respectively. No side effects were reported. These results indicate that MyrLiq® associated with other products might be playing an important role for the anti-inflammatory and analgesic activity supporting their application as a natural remedy to alleviate pain and improve quality of life in migraine patients.

For further reading on this clinical study refer to the publication:

Tonini M.C., Giordano L. (2018)
Commiphora myrra, alternative treatment in migraine prophylaxis: open label prospective pilot study.
ANeurological Sciences (2018) 39 (Suppl 1):S165–S166(read online)

MyrLiq® and pain reduction during intrauterine spiral insertion

In order to evaluate the efficacy of a new food supplement (Evandol) containing MyrLiq® in association with BosLiq® and other ingredients in pain reduction during and following the insertion of the intrauterine spiral (intrauterine device, IUD) in nullipar women, the patients took Evandol four days before the insertion of the IUD and continued for the next three days. Patients in the control group who had similar characteristics to the baseline of the Evandol group did not take Evandol. Significant differences were found between the test group and the control group in terms of pain scores during intrauterine spiral insertion. Treatment with Evandol started four days before insertion, which led to a significant reduction in pain during insertion. Evandol was able to reduce pain even in the days following insertion of the IUD, as evidenced by significantly different pain scores with respect to the control group. The study indicates that the analgesic properties of Evandol appear to eliminate pain in almost all patients, compared to the control group, as evidenced by the fact that the pain scores were zero in most patients on the third day from inclusion of the IUD, and that comparisons to T3 showed significant differences between the two groups. This observational pilot study on Evandol, a new blend based on plant extracts containing MyrLiq® and BosLiq®, could pave the way for phytotherapies to support patients who undergo intrauterine device insertion.

For more information on this clinical study, refer to the publication:

Costantino, M., Guaraldi, C., Costantino, D. (2018)
Efficacia di Evandol, un nuovo integratore alimentare contenente mirra (MyrLIQ®), boswellia (BosLIQ®) e ananas nella riduzione del dolore durante l’inserimento della spirale intrauterina in donne nullipare. Uno studio pilota osservazionale.
Giornale Italiano di Ostetricia e Ginecologia, Vol. XL – N. 3 pp. 119-124.(leggi pdf)