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Thai Herb Research

Zanthoxylum limonella Alston (Ma-Kwaen)

  1. BIOLOGICAL ACTIVITIES

 

  • Mosquito Repellent Property

Zanthoxylum limonella Alston appears to contain chemical constituents that acts Mosquito repellent and larvicidal activity.[1] Once study found that the extract of the fruits of Z. limonella is evaluated as repellent against Aedes albopictus mosquito in. All repellents have been tested at three different concentrations (10, 20 and 30 %). The fruit oil and extract provided better offered the longest duration of protection effective against mosquitoes. Repellent efficacy of 30 % concentration of fruit oil in mustard oil mixture gave the longest protection time of repellency (296 - 304 min) against A. albopictus. [2]

In another study by Trongtokit et al [3] studied the repellency of essential oil from the fruit of Z. limonella using an arm-in-cage test. The undiluted fruit volatile oil gave complete protection time for 2 hours against A. aegypti, Culex quinquefasciatus, and Anopheles dirus.

Moreover, Mostel, the repellent product by the Insecticide Research Unit, Mahidol University, Thailand, containing binary mixture of 10 % clove oil (essential oil from Syzygium aromaticum) plus 10 % makaen oil (essential oil from the fruit of Z. limonella) in a gel form gave 100 % protection for 4-5 h against A. aegypti, C. quinquefasciatus, and A. dirus by arm in cage methods [4]. Mostel provides protection against A. stephensi for 4.5-5 h by the cage test and gave protection from free flying mosquitoes in a mosquito proof room for 7-8 h [3].

  • Antimicrobial Property

Antibacterial and antifungal activities, also found in the crude chloroform extract from the fruits of Z. limonella which has been investigated in vitro and showed antituberculous activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of 200 µg/mL [5].

One study indicated interesting result of the bioactive compounds isolated from dichloromethane extract of stem of Z. limonella, dictamnine and tembamide [6] which has shown to have antitubercular activity against Mycobacterium tuberculosis H37Rv with a MIC value of 30 µg/mL [7] and shows antibacterial activity against oral pathogens, Streptococcus sanguinis, Streptococcus mutans, and Lactobacillus casei with MIC of 0.4, 0.4 and 0.1 mg/mL [8]. Moreover, it has also been shown to have antifungal activity against the plant pathogenic fungus Cladosporium cucumerinum and Pyricularia oryzae with MIC of 25 and 6.25 µg/mL [9,10]. As for Tembamide, one study also showed that (10) it also exhibits anti-HIV property with EC50 values of < 0.1 µg/mL [11].

Another study run by Tangjitjaroenkun et al [24] reported that the antibacterial activities of crude essential oil, the distilled fractions from Z. limonella fruits and pure major compounds including sabinene, limonene and terpinen-4-ol showed a potent antibacterial activity against B. subtilis, S. aureus and E. coli (> 10 mm inhibition diameter)but weak against P. aeruginosa (< 10 mm inhibition diameter).

Moreover, the crude extracts were sent to the antimalarial and antituberculous screening laboratory of BIOTEC, NSTDA for evaluation their activities [15] which showed that the crude chloroform extract exhibited antimalarial activity against Plasmodium falciparum and antituberculous activity against Mycobacterium tuberculosis H37 Ra.


  • Antioxidant Property

Free radical scavenging activity of Z. limonella essential oil from the fruits and crude dichloromethane extracts of leaves and stems conducted by Tangjitjareonkun et al [12] to study its effect on diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and trolox equivalent antioxidant capacity (TEAC). indicated e extracts and essential oil cannot provide direct protection against free radical to protect the cell membrane from the damage caused by lipid peroxidation. On the other hand, the pretreated PC-3 and DU-145 with various concentrations of SD, SM, and essential oil at 0, 0.5 and 5 µg/mL for 24 h significantly decreased the MDA level of cell lysate.

In another study by Nanasombat and Wimuttigosol [13], Z. limonella essential oil was determined by four different methods and exhibited strong antioxidant activity with IC50 value of 5.66 mg/mL (DPPH assay), 66.16 % antioxidant activity (β-carotene bleaching test), 0.26 mM/mg reducing capacity (ferric reducing antioxidant power assay), and 79.07 % (superoxide anion scavenging activity assay). In addition, the free radical scavenging activity of the aqueous seed extract of this plant was measured by TEAC assay and the TEAC value was 5.059 mM trolox/gdw [14].

In one study evaluated by DPPH scavenging assay on anti-oxidant activity, phenolic and flavonoid constituents of crude extracts Zanthoxylum limonella[17], anti-oxidant activity of Z. limonella stalk and seed extract on methanol extract showed IC50 values as 0.26 and 0.37 mg/ml, as well as total flavonoid content of stalk (25.76 gif.latex?pm 0.43 mgQE/g) and seed (10.25 gif.latex?pm 0.63 mgQE/g).


1.4 Antitumour Property

In vitro assessment of the antitumour promoting activity of methanolic fruit extract of Z. limonella was measured by the in vitro 12-Otetradecanoylphorbol-13-acetate (HPA, 40 ng/mL) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in lymphoid cell line, Raji cells. The fruit extract showed strongly inhibitory effect (IE ≥ 70 %) at 200 µg/mL. The result indicated that this extract might contain effective antitumour promoters or cancer chemopreventive agents [15].

 

  1. Gastrointestinal stimulant effect

concluded that the essential oil from the fruit of Zanthoxylum limonella possessed stimulation effect on different smooth muscle preparations by non-specific mechanisms. It involved the non-receptor and receptor-mediated mechanism. Gastrointestinal stimulant effect of the essential oil was confirmed in intact mice since the oil significantly increased black ink movement from the stomach to ileo-caecal junction after oral feeding.




References

  1. Supabphol, Roongtawan, Tangjitjaroenkun, Janpen. Chemical Constituents and Biological Activities of Zanthoxylum limonella (Rutaceae): A Review. Tropical Journal of Pharmaceutical Research. 2015; 13. 2119. 10.4314/tjpr.v13i12.25.
  2. Das NG, Baruah II, Talukdar PK, Das SC. Evaluation of botanicals as repellents against mosquitoes. J Vect Borne Dis 2003; 40: 49-53
  3. Trongtokit Y, Rongsriyam Y, Komalamisra N, Apiwathnasorn C. Comparative repellency of thirty-eight essential oils against mosquito bites. Phytother Res. 2005; 19: 303-309.
  4. Trongtokit Y, Rongsriyam Y, Komilamisra N, Krisackphong P, Apiwathnasorn C. Laboratory and field trial of developing medicinal local Thai plant products against four species of mosquito vectors. Southeast Asian J Trop Med Public Health 2004; 35: 325-333
  5. Charoenying P, Laosinwattana C, Phuwiwat W, Lomratsiri J. Biological activities of Zanthoxylum limonella Alston. fruit extracts. KMITL Sci J 2008; 8: 12-15.
  6. Simanek V. Benzophenanthridine alkaloids. In: Brossi A., editor, The Alkaloids, Chemistry and Pharmacology. London: Academic Press; 1985. pp 186-240.
  7. Huang HY, Ishikawa T, Peng CF, Tsai IL, Chen IS. Constituents of the root wood of Zanthoxylum wutaiense with antitubercular activity. J Nat Prod 2008; 71: 1146-1151.
  8. Severino VGP, Silva MFGF, Lucarini R, Montanari LB, Cunha WR, Vinholis AHC, Martins CHG. Determination of the antibacterial activity of crude extracts and compounds isolated from Hortia oreadica (Rutaceae) against oral pathogens. Braz J Microbiol 2009; 40: 535-540
  9. Zhao W, Wolfender JL, Hostettmann K, Xu R, Qin G. Antifungal alkaloids and limonoid derivatives from Dictamnus dasycarpus. Phytochem 1998; 47: 7-11.
  10. Lewis JR. Biological activity of some Rutaceous compounds. In: Waterman P.G., Grundon M.F., editors. Chemistry and Chemical Taxonomy of Rutales. London: Academic Press; 1983. pp 301-318.
  11. Chen MJ, Lee KH, Tsai IL, Chen IS. Two new sesquiterpenoids and anti-HIV principles from the root bark of Zanthoxylum ailanthoides. Bioorg Med Chem 2005; 13: 5915-5920.
  12. Tangjitjaroenkun J, Supabphol R, Chavasiri W. Antioxidant effect of Zanthoxylum limonella Alston. J Med Plants Res 2012; 6(8): 1407-1414.
  13. Nanasombat S, Wimuttigosol P. Antimicrobial and antioxidant activity of spice essential oils. Food Sci Biotechnol 2011; 20(1): 45-53.
  14. Palasuwan A, Soogarun S, Lertlum T, Pradniwat P, Wiwanitkit V. Inhibition of heinz body induction in an in vitro model and total antioxidant activity of medicinal Thai plants. Asian Pac J Cancer Prev 2005; 6: 458-463.
  15. Murakami A, Jiwajinda S, Koshimizu K, Ohigashi H. Screening for in vitro anti-tumor promoting activities of edible plants from Thailand. Cancer Lett 1995; 95: 139-146.
  16. Charoenying, Patchanee & Laosinwattana, Chumroon & Phuwiwat, Wirat. (2008). Biological activities of Zanthoxylum limoneïla Alston fruit extracts. KMITL Sci. J.. 8.
  17. Phowichit S, Anti-oxidant activity, phenolic and flavonoid constituents of Crude extracts Piper ribesioides and Zanthoxylum limonella traditional herbal medicine in Northern Thailand. RMUTT Research Journal Rajamangala University of Technology Thanyaburi 2019;

Clinical Study of Kaempferia parviflora (Black Ginger)

Kaempferia parviflora (Black Ginger) is perennial herb included in a family of Zingiberaceae. The plant has its origin in Thailand, locally referred as “Krachai Dum”. Among local people, Kaempferia parviflora has been recognized as health-promoting herbs since it is loaded with a wide range of medical and nutritional benefits which is commonly used to treat metabolic ailments and improve vitality. Rich in an aphrodisiac compound, the plant also has a reputation for its excellent tonic effect to relieve impotent symptoms. It contains polymethoxyflavones (PMFs) which are flavonoids that exhibit various bioactivities, such as, anti-inflammatory, antioxidant, anticancer, muscular metabolism enhancing, anti-photoaging and phosphodiesterase (PDE)5 inhibitory, anti-cardiovascular disease, and viral protease inhibitory activities.

Here’s a synopsis of the latest clinical studies on Kaempferia parviflora and what they revealed:

Physical Improvement

Contained with polymethoxyflavones (PMFs), Kaempferia parviflora is reported to increased energy production by activating AMP-activated protein kinase (AMPK) in C2C12 myoblasts.[1] On physical fitness performance and muscular endurance of KPE effect in male mice, after 4 weeks oral treatment, KPE showed significant improvement on swimming time, motility after swimming, and grip strength.

Researchers at Oryza Oil & Fat Chemical Co., Ltd investigated the effects of black ginger extract (KPE) rich in polymethoxyflavones on physical fitness and fatigue [2]. This 11-week studied 24 healthy volunteers which were given 30 mg of Kaempferia parviflora daily for 4 weeks. Tested by physical fitness test, questionnaire and blood test, after a 4-week period, results indicated improvement in physical fitness, in left hand grip strength performance. Also, in the evaluation the effects of KPE on fatigue analyzed by 5-m tandem walking, cycle ergometer test, in all participants, the daily fatigue score at the conventional state was slightly decreased after 4-week intake of KPE.

Another 8 weeks trial was conducted with 45 healthy elderly volunteers which had been randomized to receive placebo or K. parviflora extract at doses of 25 or 90 mg once daily. Physical performance using 30 sec chair stand test, hand grip test, 6 min walk test, and tandem test were used a baseline data of analysis to evaluate lower and upper -body muscular strength as well as the cardio-pulmonary endurance.

All assessments were performed every 4 weeks throughout the 8-week study period [3]. The results showed that K. parviflora increased performance in 30-second chair stand test and 6 min walk test together with the increased all scavenger enzymes activities and the decreased MDA level. Therefore, K. parviflora can enhance physical fitness partly via the decreased oxidative stress. In conclusion, K. parviflora is the potential health supplement for elderly. However, further study is required.

Moreover, another initial clinical trials of KP extract on 60 soccer players have demonstrated that at 180 mg/day dose for 12 weeks, it significantly enhanced physical fitness, increased muscle strength, and improved aerobic capacity in soccer players[4].The data was collected by using 6 physical performance test including, a sit-and-reach test, a hand grip strength test, a back-and-leg strength test, a 40-yard technical test, a 50-metre sprint test, and a cardiorespiratory fitness test.

Male Enhancement

Pilot trial aimed to examine the effects of an ethanol extract of the K. parviflora rhizome, on erectile function in healthy middle-aged and older men revealed interesting result on its potential erectile dysfunction activity [5]. The study was determined via the International Index of Erectile Function (IIEF) as well as subjects’ sexual satisfaction using the Global Assessment Questions (GAQ) about erectile function. 14 generally healthy males aged 50-68 years with self-reported mild erectile dysfunction, who were not using prescription treatments were supplemented with 100 mg KPE supplement for 30 days.

According to the authors, supplementation with K. parviflora rhizome resulted in “statistically significant improvements in erectile function, intercourse satisfaction, and total scores on the IIEF questionnaire.” The supplement itself was also found to be safe and well-tolerated.

An 8-week double-blind, placebo-controlled, randomized trial was conducted to study the effect of KP extract administration on erectile response of male elderly volunteers [6]. Each participant received one capsule of placebo or KP extract at dose of 25 and 90 mg once daily. The erectile function tests including the response latency time to visual erotic stimuli, size and length of penis both in flaccid and erection states were assessed after single administration. After 1 and 2 months of treatment with KP at a dose of 90 mg day experienced a statistically significant increase in the length and width of their penis both in flaccid and erection states.

Further study showed 3,5,7,3',4'-pentamethoxyflavone (PMF) at 0.3mM was able to relax pre-contracted human cavernosal strips from 100% contraction to 1.63+/-0.62%, and this was not inhibited with a cGMP inhibitor (ODQ), potassium channel blocker (TEA), nor an ATP channel blocker (glybenclamide);[7] In a test of PDE5 inhibition, PMF failed to augment glyceryl trinitrate-induced relaxation while Viagra was effective.[7] These results suggest the relaxing effects of PMF on the penis tissue are not mediated by NO, cGMP, nor potassium channels (common mechanisms of action for other drugs) and is unlikely to be a Rho-Kinase inhibitor, but appears to be a calcium channel inhibitor but may act by other (currently unknown) mechanisms.[7]

One study in sexually mature rats given 70mg/kg bodyweight Kaempferia parviflora daily noted that supplementation was able to increase mounting frequency and reduce ejaculatory latency (indicative of aphrodisiac effects) and was nonsignificant additive with exercise; post ejaculatory latency was seemingly unaffected.[8] Interestingly, one study using a higher dose (240mg/kg) noted inhibitory effects on aphrodisia in rats[9] and one using 1g/kg noted no significant differences between groups.[10]

PDE5 inhibitors

Other constituents of Kaempferia parviflora appear to be PDE5 inhibitors (similar to Viagra and Horny Goat Weed's Icariin).[11] Tested by the extract itself at 50ug/mL, Kaempferia parviflora rhizome was able to inhibit 62.63+/-7.17% of PDE5 inhibitory value (out of 41 tested herbs, only Caesalpinia sappan stem (60.23+/-1.81%), Senna surattensis leaf (65.08+/-0.78%), Acacia auriculaeformis leaf (73.66+/-4.87%) and Boesenbergia rotunda rhizome (40.86+/-3.94%) were similar); K.Parviflora had an IC50 of 12.24+/-0.99ug/mL with the ethanolic extract.[11] Isolated compounds and their individual PDE5 IC50 values are 10.64+/-2.09ug/mL (DMF), 37.38+/-1.15ug/mL (2,7,4'-trimethoxyflavone), 16.32+/-1.93ug/mL (3,5,7-trimethoxyflavone), and 30.41+/-2.34ug/mL (PMF); all underperforming relative to Viagra.[11]

Anti-obesity Effect

In an 8-week study of obese (TSOD) and lean (TSNO) mice given 1% or 3% of their feed as Kaempferia Parviflora indicated that supplementation at either dose was able to preserve reaction latency to a pain test but only in the obese group; the authors hypothesized that TSOD obese mice developed diabetic neuropathy and that Kaempferia Parviflora attenuated these changes.[12] The only human study to assess pain was a human study measuring the Rate of Perceived Exertion (RPE) on an exercise test, and found no effect with an acute bolus of 1.35g.[13]


In castrated male rats given 1,000mg/kg Kaempferia parviflora daily for 5 days, an increase of serum testosterone occurred independent of any changes in LH, Progesterone, or FSH and to the degree of 66% higher than control.[14] Another study in adult male rats (not castrated) also failed to note significant changes to LH and FSH, while testosterone trended to be non-significantly reduced; oddly, this study noted an increase in the weight of the prostate but not levator ani (mixed results on androgenicity independent of serum testosterone).[15]













References

  1. Toda, Kazuya and Hitoe, Shoketsu and Takeda, Shogo and Shimoda, Hiroshi. "Black ginger extract increases physical fitness performance and muscular endurance by improving inflammation and energy metabolism." Heliyon (2016): 115.
  2. Kazuya Toda, Marina Kohatsu, Shogo Takeda, Shoketsu Hitoe, Norihito Shimizu, and Hiroshi Shimoda. "Enhancement of physical fitness by black ginger extract rich in polymethoxyflavones: a double-blind randomized crossover trial." Integrative Molecular Medicine (2016): 628-634.
  3. Wattanathorn J et al., “Positive Modulation Effect of 8-Week Consumption of Kaempferia parviflora on Health-Related Physical Fitness and Oxidative Status in Healthy Elderly Volunteers,” Evidence-based complementary and alternative medicine, (2012).
  4. Promthep K, et al., "Effect of Kaempferia parviflora Extract on Physical Fitness of Soccer Players: A Randomized Double-Blind Placebo-Controlled Trial." Medical science monitor basic research, (2015).
  5. Wannanon P et al., “Efficacy assessment of Kaempferia parviflora for the management of erectile dysfunction,” Online Journal of Biological Sciences, vol. 12, no. 4 (2012): 149-155
  6. Stein RA et al., “Kaempferia parviflora ethanol extract improves self-assessed sexual health in men: a pilot study," Journal of Integrative Medicine, (2018).
  7. Jansakul C, et al., "Relaxant mechanisms of 3, 5, 7, 3', 4'-pentamethoxyflavone on isolated human cavernosum." Eur J Pharmacol, (2012).
  8. Chaturapanich G, et al., "Enhancement of aphrodisiac activity in male rats by ethanol extract of Kaempferia parviflora and exercise training". Andrologia, (2012).
  9. Chaturapanich G, et al., "Effects of Kaempferia parviflora extracts on reproductive parameters and spermatic blood flow in male rats". Reproduction. (2008).
  10. Sudwan P, et al., "Effect of Kaempferia parviflora Wall. ex. Baker on sexual activity of male rats and its toxicity". Southeast Asian J Trop Med Public Health. (2006).
  11. Temkitthawon P, et al., "Kaempferia parviflora, a plant used in traditional medicine to enhance sexual performance contains large amounts of low affinity PDE5 inhibitors". J Ethnopharmacol. (2011).
  12. Akase T, et al., "Antiobesity effects of Kaempferia parviflora in spontaneously obese type II diabetic mice". J Nat Med. (2011).
  13. Wasuntarawat C, et al., "No effect of acute ingestion of Thai ginseng (Kaempferia parviflora) on sprint and endurance exercise performance in humans". J Sports Sci. (2010)
  14. Trisomboon H, et al., "Effect of daily treatment with Thai herb, Kaempferia parviflora, in Hershberger assay using castrated immature rats", J Reprod Dev. (2007)
  15. Trisomboon H, et al., "Oral administration of Kaempferia parviflora did not disturb male reproduction in rats". J Reprod Dev. (2008)






















Butea Superba

  1. Erectile Dysfunction

                Faculty of Science from Chulalongkorn conducted a study the effect of Butea superba on erectile dysfunction (ED) in Thai males. A 3-month randomized double-blind clinical trial was carried out in volunteers with ED, aged 30 years approximately 70 years, to evaluate the therapeutic effect of the crude preparation of Butea superba tubers on ED by using IIEF-5 questionnaire. Participants were given 1000 mg/day Butea Superba. Estimation of the sexual record indicated that 82.4% of the patients exhibited noticeable improvement. Haematology and blood chemistry analysis revealed no apparent change.[1] The results also showed that patients with additional health problems, such as diabetes mellitus, hyper-tension, heart disease and hyperthyroidism, responded satisfactorily to B. superba.[1]

 

  • Butea Superba Compared to Sildenafil for Erectile Dysfunction treatment

                At study conducted by researchers at University Hospital ‘Dr Jose E. Gonzalez used Butea Superba to compare with Sildenafil (a phosphodiesterase‐5 inhibitor) for erectile dysfunction treatment.[2]

                The study was carried by 32 men with erectile dysfunction ranging from 42-78 years old evaluated by using the International Index of Erectile Function 5 (IIEF‐5). One subjects group were treated orally with Butea Superba 100 mg and the others were supplemented with 50 mg. of Slidenafil. 

                After a 1‐week wash‐out, responders to BS received either 100 mg starch or 100 mg of another batch of BS (double‐blind). 84% of patients in the BS group responded positively, compared with 26 (81%) in the sildenafil group.[2] When assessing IIEF scores alone, 12 (38%) had a better score after BS, seven (22%) after SF, and eight (25%) had same score. However, no side effects were recorded.

                In an another open-label trial for persons taking 100mg of Butea Superba noted that the proerectile effects of the herb, when taken 1-2 hours before sex, was comparable to the active control of Viagra; when the study was conducted in a double-blind manner using a different batch of Butea Superba, these effects failed to be replicated.[2] The authors noted a higher degree of variation between batches, and stated that blending of PDE5 inhibitors in the first batch caused a false positive.[2]

  • Butea Superba on Penile Erection in Rats

                Butea Superba has been reported to influence penile erection in rats at a concentration of 0.1-1000mg/mL (in vitro testing on rat penile tissue) where the mean cavernosal pressure increased at 0.1mg/mL (1.7%), 1mg/mL (6.8%), 10mg/mL (4.2%) and 1000mg/mL (8.3%); somewhat following concentration-dependence.[3] When measuring intracavernosal pressure (ICP), a concentration correlating to 1mg/kg was seen as most effective, and the relaxation effect of Butea Superba seems to be potentiated when incubated with cGMP (a small signaling molecule that is the result of PDE5 inhibition).[4] This penile erection property has been replicated in diabetic rats (diabetes tends to hinder erectile function secondary to poor blood circulation) with 10mg/kg of the ethanolic extract being the most effective dose (relative to 1mg/kg and 100mg/kg, although all were better than control)[5] and although one study has once reported a potency greater than Viagra, it itself failed to replicate these effects.[2]

  1. Fertility

One investigated conducted by Faculty of Medicine, Chiang Mai University [9] about the long-term effects of ethanolic extracts of Butea superba root on sperm number and fertility, sperm quality and histology of testis in male hamsters evaluated by counting the number of sperm, and the number of intact acrosomes on the sperm head. Results suggested that fed with alcoholic extract suspensions of B. superba root at doses of 0.1, 1 or 10 mg/kg BW/day for 6 months, the sperm count was increased in the treated male hamsters in a dose-dependent manner.

 

  • Sperm Motility and Concentration

Butea Superba is also reported to may be useful in fertilization according to Jeenapongsa et. al [6]. In a study aimed to investigate effects of chronic treatment of B. superba on sperm motility and concentration in rats and mice in correlation with testicular damage, results indicated that after 6 months of orally administered distilled water or B. superba alcoholic extract (0.01, 0.1 or 1.0 mg/kg BW/day), a long-term treatment with B. superba extract significantly increased the sperm concentration and delayed the decreased motility with time. The author concluded that chronic use of B. superba increases the number of sperm, prolongs, sperm motility in vitro while produces no changes on sperm morphology [6].

In another study, powdered crude drug at the doses of 2, 25, 250, and 1250 mg/kg body weight was administered for 8 weeks; there was an increased testis weight and sperm counts in rat [7].

  • Antidepressant-like Effect

The effect of Butea Superba on depression-like behavior in mice subjected was examined to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of Butea Superba and the molecular mechanism underlying this effect. Mice were administrated with 300 mg of dried herb weight/kg, p.o daily [8]. Results suggested that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by restoring dysfunctions of the HPA axis and synaptic plasticity-related signaling systems and neurogenesis in the hippocampus [8].


 

 

References

  1. Cherdshewasart W, Nimsakul N. Clinical trial of Butea superba, an alternative herbal treatment for erectile dysfunction. Asian J Androl. 2003.
  2. Cortés-González JR, et al. The use of Butea superba (Roxb.) compared to sildenafil for treating erectile dysfunction. BJU Int. 2010.
  3. Nuengchamnong N, et al. HPLC coupled on-line to ESI-MS and a DPPH-based assay for the rapid identification of anti-oxidants in Butea superba. Phytochem Anal. 2005.
  4. Tocharus C, Smitasiri Y, Jeenapongsa R. Butea superba Roxb. enhances penile erection in rats. Phytother Res. 2006
  5. Tocharus C, et al. Butea superba (Roxb.) improves penile erection in diabetic rats. Andrologia. 2012.
  6. Tocharus, Chainarong & Jeenapongsa, Rattima & Teakthong, Thanasak & Smitasiri, Yuthana. Effects of Long-term Treatment of Butea superba on Sperm Motility and Concentration. 2005. 13.
  7. Manosroi A, Sanphet K, Saowakon S, Aritajat S, Manosroi J. Effects of Butea superba on reproductive systems of rats. Fitoterapia. 2006;77(6):435–438.
  8. Mizuki, Daishu & Matsumoto, Kinzo & Tanaka, Ken & Le, Xoan & Fujiwara, Hironori & Ishikawa, Tsutomu & Higuchi, Yoshihiro. Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action. Journal of ethnopharmacology. 2014
  9. Tocharus C., Shimbhu D., Tocharus J., Ruchiratanti-angkoor, Ruchiratanti-angkoor A., Effect of Butea Superba. Roxb root extract on male hamster fertility. Chiang Mai Med J 2012;51(2):39-44.





Eurycoma Longifolia


  1. Adaptogens
    • Stress Hormone

63 subjects (32 men and 31 women) was screened for moderate stress and supplemented with a standardized hot-water extract of Eurycoma longifolia root or Placebo (PL) for 4 weeks [2].  Significant improvements were found in the TA group for Tension (−11%), Anger (−12%), and Confusion (−15%). Stress hormone profile (salivary cortisol and testosterone) was significantly improved by Eurycoma longifolia (Tongkat ali) supplementation, with reduced cortisol exposure (−16%) and increased testosterone status (+37%). Results suggested that daily supplementation with Eurycoma longifolia root extract improves stress hormone profile and certain mood state parameters, suggesting that it may be an effective approach to shielding the body from the detrimental effects of “modern” chronic stress, which may include general day-to-day stress, as well as the stress of dieting, sleep deprivation, and exercise training [2].

  1. Aphrodisiac activities

Ang and Sim [3] investigated the effects of E. longifolia roots extracts (chloroform, methanol, water and butanol) on the libido of sexually experienced male rats treated with various doses (200, 400 and 800 mg/kg BW, 2 times daily for 10 days). The results revealed that a dose-dependent increase in mounting frequency of the treated animals with 400 mg/kg of chloroform, methanol, water and butanol fractions resulting in mounting frequencies of 5.3+/−1.2, 4.9+/−0.7, 4.8+/−0.7 and 5.2+/−0.1, and 800 mg/kg respectively, with no erections, intromissions, ejaculations or seminal emissions during the 20-min observation period [3]. From the obtained results they concluded that E. longifolia is a potent stimulator of sexual arousal in sexually vigorous male rats with the absence of feedback from genital sensation [3].

Sexual motivation activity in adult, middle-aged male mice and in retired breeders, after administering E. longifolia root extract (500 mg/kg in chloroform, methanol, butanol, and water; for control, 3 ml/kg of normal saline+ 30 mg/kg of yohimbine daily for 10 d) have been reported by Ang et al. [4]. Their results showed a momentary increase in the percent of male mice responding after consumption of the fractions with 50% of the adult middle-aged male mice treated with E. longifolia [4].

In vivo study on sexual motivation on sexually naïve 400 male albino mice subjected to training protocol for 10 consecutive days [5], Transient increase in the percentage of male mice responding to the right choice after consumption of EL extracts. Enhanced sexual motivation was noticed after 3 days of treatment with EL extracts. Also, the effect was more prominent after eight days of treatment with EL [5].

In another vivo study of Initiation of sexual performance on inexperienced castrated adult male Spraguedawley rats, subjects were orally given 200, 400, 800 mg/kg (twice daily) for 10 days prior to the test, and continued throughout the test [6]. The positive control group was given testosterone subcutaneously at 15 mg/kg daily. Negative control group received saline. Treated groups were given EL extracts at 50-80 d post-castration. Results showed that a dose-dependent increased in sexual performance with EL supplementation but lower compared to testosterone group. EL promoted growth of sexual accessories (at 800 mg/kg EL) but was less than testosterone group. In conclusion, E. longifolia enhanced initiation of sexual performance of inexperienced castrated male rats. Therefore, E. longifolia has aphrodisiac effects [6].

In vivo animal study of aphrodisiac evaluation on sexually sluggish adult male Spraguedawley rats by Zanoli a et. la [7], groups of 8 animals each were submitted to three different types of treatment: (1) acute at 3 dose levels (250, 500 and 1000 mg/kg); (2) subacute (daily for 6 days) at the dose of 500 mg/kg and (3) subchronic (daily for 12 days) at the same dose (500 mg/kg) evaluated by recording mount, intromission and ejaculation latencies and post-ejaculatory interval. After the test, testosterone serum levels were increased in rats subacutely treated in comparison with controls. in addition, the subacute administration reduced post-ejaculatory interval. In impotent rats both subacute and subchronic treatments increased the percentage of mounting and ejaculating rats [7].


  • Erectile Function Improvement

In a human study of Standardized water-soluble extract of Eurycoma longifolia (Tongkat ali) as testosterone booster for managing men with late-onset hypogonadism [1], 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardized water-soluble extract of Tongkat ali for 1 month. The Ageing Males’ Symptoms (AMS) was used as a standardized rating scale. Results revealed that treatment of late-onset hypogonadism patients with this Eurycoma longifolia (Tongkat ali) extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration. In addition, before treatment only 10.5% of the patients did not show any complaint according to the AMS scale and 35.5% had normal testosterone levels, after the completed treatment 71.7% and 90.8% of the patients showed normal values, respectively [1].



References

  1. Tambi, Mohd & Musa, Kamarul Imran & Henkel, Ralf. (2011). Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism?. Andrologia. 44 Suppl 1. 226-30. 10.1111/j.1439-0272.2011.01168.x.
  2. Talbott, Shawn & Talbott, Julie & George, Annie & Pugh, Mike. (2013). Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. Journal of the International Society of Sports Nutrition. 10. 28. 10.1186/1550-2783-10-28.
  3. Ang HH, Sim MK. Eurycoma longifolia Jack enhances libido in sexually experienced male rats. J Exp Anim Sci 1997;46:287–90.
  4. Ang, Hooi & Lee, Kheng & Kiyoshi, Matsumoto. (2003). Eurycoma longifolia Jack Enhances Sexual Motivation in Middle Aged Male Mice. Journal of basic and clinical physiology and pharmacology. 14. 301-8. 10.1515/JBCPP.2003.14.3.301
  5. Ang HH, Chan KL, Gan EK, Yuen KH. Enhancement of sexual motivation in sexually naive male mice by Eurycoma longifolia. Int J Pharmacogn 1997;35:144-6.
  6. Ang HH, Cheang HS, Yusof APM. Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of inexperienced castrated male rats. Exp Anim 2000;49:35-8.
  7. Zanoli, P & Zavatti, Manuela & Montanari, C & Baraldi, M. (2009). Influence of Eurycoma longifolia on the copulatory activity of sexually sluggish and impotent male rats. Journal of ethnopharmacology. 126. 308-13. 10.1016/j.jep.2009.08.021

Pueraria Mirifica

  1. Sources of Miroestrol

According to various researches and reviews, Pueraria Mirifica is reported to exhibit an abundance of flavonoids and that includes miroestrol which is known to offer great amount of health benefits, especially among women. The plant is a rich source of phytoestrogen eg. genistein, daidzein, puerarin, mirificin, miroestrol and isomiroestrol2.

Several Studies showed that the highest potency of an estrogenic-like antioxidant from Pueraria candollei Wall. Ex Benth var. mirifica like miroestrol and isomiroestrol, might be powerful tools for future studies on neuroprotective and estrogen function.

1.2 Hair Growth Prevention

                One research published on Key Engineering Materials pointed out how significant Pueraria Mirifica can do to hair growth [1]. Objective of the study was to develop solid lipid nanoparticles containing Pueraria Mirifica ethanolic extract on hair promotion.

Result shows that "PM extract was a good safety herbal extract, which no cytotoxicity at the concentrations from 1 to 1,000 μg/ml. The cell proliferation of PM extract treated HFDPCs significantly increased in a dose-dependent manner, indicating the possibility to promote hair growth at the concentrations from 10 to 100 μg/ml"[1]. PM extract-loaded SLN might be an effective formulation for hair growth disorders treatment.[1]

1.3 Grey Hair Prevention

                Grey hair can bother many women and men as it is a sign of aging. Pueraria mirifica were also reported to be effective for hair grey prevention [2]. One randomized, double-blind clinical trial is conducted to study the efficacy of Pueraria Lobata on grey hair prevention using the phototrichogram analysis with 44 female subjects. The participants were randomly given with either APHG-1001 or placebo twice daily for 24 weeks.

            An example of counting new gray hair developed during the treatment using the phototrichogram analysis. This clinical trial revealed that APHG-1001, which contains an extract of P. lobata, could prevent the development of new gray hair without any remarkable adverse effects. Thus, it can be considered as a viable treatment option for the prevention of gray hair [2].

1.4 Vagina Health

One study by Manonai et. al [3] aimed to see the effect of Pueraria mirifica on vaginal symptoms, vaginal health index, vaginal pH, and vaginal cytology in healthy postmenopausal women indicated interesting results. All participants were orally administrated with 20, 30, or 50 mg of Pueraria mirifica in capsules for 24 weeks and after the treatment, vaginal dryness symptom significantly decreased after 12 weeks of treatment in which the author concluded that Pueraria mirifica is proven to exhibit estrogenicity on vaginal tissue, to alleviate vaginal dryness symptoms and dyspareunia [3].

Several evidences indicated that the estrogenic activity of P. mirifica on the reproductive system was confirmed by the suppression of pituitary gonadotropin and inhibin (INH) secretion in both female and male mice and rats, and in female monkeys [6], [7], [8], [9], [10], [11], [12].

1.4.1 Sexual skin coloration

A 30-day pre-treatment period, 90-day treatment period, and 60-day post-treatment period were conducted to investigate the estrogenic effect of Pueraria mirifica (PM) on sexual skin coloration in cynomolgus monkeys [28]. Aged menopausal monkeys were divided into three groups. Each group (n=3) was fed 10, 100, or 1,000 mg of PM daily. The results show that the sexual skin exhibited reddish coloration within 24 hours after PM-treatment and remained this way for the first half of the PM-feeding period. The changes in sexual skin coloration were not dose-dependent. The present results indicate that PM had estrogenic action by increasing reddish sexual skin coloration in aged menopausal monkeys [28].

1.5 Hormone Replacement

Due to the suppression of the secretion of luteinizing hormone (LH), FSH and INH in female cynomolgus monkeys, experimental animals which have a broadly similar hormonal pattern and reproductive system to those of humans, Pueraria mirifica could become an alternative choice for a contraceptive drug in reproductive women. Indeed, Pueraria mirifica has been reported to suppress folliculogenesis and ovulation [ 10, 23].

1.6 Menopausal Symptoms

In another study conducted by Virojchaiwong et. al [4] to compare between Pueraria mirifica 25 and 50 mg for menopausal symptoms for 6 months, both dosage of Pueraria mirifica were similarly effective and safe in the treatment of menopausal symptoms. Pueraria mirifica also demonstrated great promise in the treatment of climacteric symptoms among perimenopausal women.[5]

Another clinical trial, involving to the estrogenic effects of the crude drug derived from dry powder of a phytoestrogen-rich Thai herb Pueraria mirifica (White Kwao Krua) in five female volunteers with menopausal symptoms, showed that the crude drug clearly improved the signs and symptoms related to menopause such as, hot flushes, frustration, sleep disorder, skin dryness, high blood cholesterol, oligomenorrhoea and amenorrhoea; with no change in cells, liver and kidney functions, as well as other physiological status after four months of treatment [19]. In four volunteers, treatment was continued to complete a one-year test period with half the dose and was found to maintain their satisfied menopausal relief status. The crude drug dosage was administered at 200 mg daily for three weeks a month during the first four months to treatment and 200 mg every other day for 20 days per month for the remaining eight months. These doses were effective and safe as phytoestrogen treatment of menopausal symptoms [19].


1.7 Alzheimer’s disease

As estrogen play important roles in the pathoetiology of Alzheimer’s disease (AD), one study has evaluated the effects of phytoestrogen extracted from Pueraria candollei, miroestrol and isomiroestrol, on factors related Alzheimer’s disease [13] by investigating for free radical scavengingand acetylcholinesterase (AChE) inhibitory activity in vitro. The interaction between the test compounds and alpha estrogenic receptor (ERĮ) was also studied using molecular modeling techniques.

1.8 Osteoporosis

Estrogen plays an immense role in bone homeostasis [17] which regulates bone homeostasis directly via acting on the bone cells, and indirectly on the immune system and oxidative stress [18]. As the loss of serum estrogen levels during menopause has been reported to cause a decrease in the bone mineral density (BMD) and bone mineral content (BMC), thus estrogen shortage is a major factor in the development of osteoporosis in postmenopausal women.

Initial research revealed that Pueraria mirifica crude powder could prevent bone loss, both in terms of the BMD and BMC, in trabecular and cortical bones of the 4th lumbar vertebra, tibia and femur in ovariectomized female and orchidectomized male rats [20, 23]. 

In this study, 6-month-old female rats were ovariectomized, kept for 4 weeks to induce bone loss, divided into five groups, and treated with Pueraria mirifica at doses of 0, 5, 25, and 50 mg/kg BW/day (PM0, PM5, PM25, and PM50 groups, respectively) or 7 mg/kg BW/day of puerarin (PU group) for 12 weeks. Only the trabecular bone mineral densities (BMDs) of tibia metaphysis (at the 12th, 14th, and 16th week) and total and trabecular BMDs of L4 (at the 16th week) of the PM50 group were significantly higher than those of the PM0 group. The study indicated that Pueraria mirifica could be used as an anti-osteoporotic agent for postmenopausal women. Since Pueraria mirifica could mainly retain bone mass at the levels before bone loss is initiated, the use of other anabolic agents in combination with P. mirifica is recommended for osteoporotic patients [27].

To confirming these effects in sex hormone deficient rats, Pueraria mirifica intake was reported to decrease serum parathyroid hormone and calcium levels in aged menopausal monkeys [21].

Although the mechanism of Pueraria mirifca action on bone cells is not been clearly understood. However,” it seems to reduce the bone turnover rate, because serum levels of bone-specific alkaline phosphatase or alkaline phosphatase (a marker of bone formation) were reduced in Pueraria mirifica treated post-menopausal women” [22, 23], while phytoestrogens have been reported to have anabolic effect on bone metabolism [24, 25]. In bone cell culture, genistein induced a significant increase in the calcium content and alkaline phosphatase activity. Genistein and daidzein caused a significant increase in the proliferation of the mouse osteoblastic cell line MC3T3-E1, as well as an increased alkaline phosphatase activity and DNA content [26].

1.9 Breast Growth & Cancer

One studies have been conducted at the Obstetrics and Gynecology Department at the Phramongkutklao College of Medicine, in Bangkok, Thailand and in Atlanta, Georgia, USA at the Emory University School of Medicine, concerning breast cell lines and Pueraria Mirifica activity in vitro. These studies have demonstrated that the rhizome extract of Pueraria Mirifica has effective anti-estrogenic properties against aggressive breast cancer lines in vitro, particularly against the estrogen receptor-positive (ER+) breast cancer lines T47-D, MCF-7, and ZR-75-1). In these studies, extract of Pueraria Mirifica has been found to promote fibrocytes within normal cells of the breasts and to restrict the growth of breast cancer cells that are dependent on estrogen.

1.10 Muscle Strength

In study involving with Pueraria mirifica Extract effect on ovariectomized rats to prevented muscle atrophy and restored muscle strength [29], adult female Wistar rats were divided into six groups: Sham-operated (SHAM); ovariectomized (OVX) fed with distilled water (PM0); OVX injected with 40 µg/kg estradiol benzoate (E40); (4-6) OVX fed with ethanolic extract of PM at doses of 50 (PM50), 500 (PM500) and 1000 (PM1000) mg/kg for 90 days. The study indicated that the estrogenic activity of PM alleviated muscle atrophy and built up muscle strength and endurance. Thus, the 50 and 500 mg/kg of PM were suitable for treating estrogen dependent sarcopenia in ovariectomized rats.


 

 

 

 

References

  1. Tansathien, K., Nuntharatanapon, N., Jaewjira, S., Pizon, J. R. L., Opanasopit, P., & Rangsimawong, W. (2019). Solid Lipid Nanoparticles Containing Pueraria mirifica Ethanolic Extract for Hair Growth Promotion. Key Engineering Materials, 819, 175–180. https://doi.org/10.4028/www.scientific.net/kem.819.175
  2. Jo, S. J., Shin, H., Paik, S. H., Na, S. J., Jin, Y., Park, W. S., … Kwon, O. S. (2013). Efficacy and Safety of Pueraria lobata Extract in Gray Hair Prevention: A Randomized, Double-Blind, Placebo-Controlled Study. Annals of dermatology, 25(2), 218–222.
  3. Manonai, Jittima & Chittacharoen, Apichart & Theppisai, Urusa & Theppisai, Hathai. (2007). Effect of Pueraria mirifica on vaginal health. Menopause (New York, N.Y.). 14. 919-24. 10.1097/gme.0b013e3180399486.
  4. Virojchaiwong, Phongthorn & Suvithayasiri, Visut & Itharat, Arunporn. (2011). Comparison of Pueraria mirifica 25 and 50 mg for menopausal symptoms. Archives of gynecology and obstetrics. 284. 411-9.
  5. Lamlertkittikul, Surachai & Chandeying, Verapol. (2004). Efficacy and Safety of Pueraria mirifica (Kwao Kruea Khao) for the Treatment of Vasomotor Symptoms in Perimenopausal Women: Phase II Study. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 87. 33-40.
  6. Trisomboon H, Malaivijitnond S, Watanabe G, Taya K. Ovulation block by Pueraria mirifica: a study of its endocrinological effect in female monkeys. (2005) Endocrine;26(1): 33-39.
  7. Trisomboon H, Malaivijitnond S, Watanabe G, Cherdshewasart W, Taya K. The estrogenic effect ofPueraria mirifica on gonadotrophin levels in aged monkeys. (2006)Endocrine. 29(1): 129-134.
  8. Malaivijitnond S, Kiatthaipipat P, Cherdshewasart W, Watanabe G, Taya K. Different effects of Pueraria mirifica, an herb containing phytoestrogens, on LH and FSH secretion in gonadectomized female and male rats. (2004)J Pharmacol Sci. 96(4): 428-435.

9.Jaroenporn S, Malaivijitnond S, Wattanasirmkit K, Trisomboon H, Watanabe G, Taya K, Cherdshewasart W. Effects of Pueraria mirifica, an herb containing phytoestrogens, on reproductive organs and fertility of adult male mice. (2006;) Endocrine. 30(1): 93-101.

  1. Trisomboon H, Malaivijitnond S, Watanabe G, Taya K. Estrogenic effect of Pueraria mirifica on the menstrual cycle and hormones related ovarian function in cyclic female cynomolgus monkeys. J Pharmacol Sci. (2006); 94(1): 51-59.
  2. Trisomboon H, Malaivijitnond S, Cherdshewasart W, Watanabe G, Taya K. The influence of Pueraria mirifica herb containing phytoestrogens on the urinary gonadotropin and estradiol levels in aged menopausal monkeys. (2007) Anim Sci J. 78(4): 378-386.
  3. Trisomboon H, Malaivijitnond S, Cherdshewasart W, Watanabe G, Taya K. Assessment of urinary gonadotropin and steroid hormone profiles of female cynomolgus monkeys after treatment with Pueraria mirifica. (2007) J Reprod Dev. 53(2): 395-403.
  4. Sukhano W, Boonyarat C, Monthakantirat O, Effects of Miroestrol and Isomiroestrol on Neuroprotective Activities Related to Memory Deficit.
  5. Muangman V, Cherdshewasart W. Clinical trial of the phytoestrogen-rich herb, Pueraria mirifica as a crude drug in the treatment of symptoms in menopausal women. (2001) Siriraj Hosp Gaz. 53(5): 300-310
  6. Chand eying V, Lamlertkittikul S. Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women. (2007) J Med Assoc Thai. 90(7): 1274-1280.
  7. Chand eying V, Sangthawan M. Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study. (2007) J Med Assoc Thai. 90(9): 1720-1726.
  8. Compston JE. Sex steroids and bone. (2001) Physiol Rev. ;81(1): 419-447.
  9. Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. (2006) J Clin Invest. 116(5): 1186-1194.
  10. Muangman V, Cherdshewasart W. Clinical trial of the phytoestrogen-rich herb, Pueraria mirifica as a crude drug in the treatment of symptoms in menopausal women. (2001) Siriraj Hosp Gaz, 53(5): 300-310 
  11. Urasopon N, Hamada Y, Cherdshewasart W, Malaivijitnond S. Preventive effects of Pueraria mirifica on bone loss in ovariectomized rats. (2008) Maturitas. 59(2): 137-148.
  12. Trisomboon H, Malaivijitnond S, Suzuki J, Hamada Y, Watanabe G, Taya K. Long-term treatment effects of Pueraria mirifica phytoestrogens on parathyroid hormone and calcium levels in aged menopausal cynomolgus monkeys. (2004), J Reprod Dev. 50(6): 639-645. DOI:10.1262/jrd.50.639 .
  13. Manonai J, Chittacharoen A, Udomsubpayakul U, Theppisai H, Theppisai U. Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women. (2008) Menopause;15(3): 530-535.
  14. Malaivijitnond S. Medical applications of phytoestrogens from the Thai herb Pueraria mirifica. (2012) Frontiers of Medicine, 6(1): 8-21
  15. Yamaguchi M, Gao YH. Inhibitory effect of genistein on bone resorption in tissue culture. (1998) Biochem Pharmacol. 55(1): 71-76.
  16. Gao YH, Yamaguchi M. Anabolic effect of daidzein on cortical bone in tissue culture: comparison with genistein effect. (1999) Mol Cell Biochem. 194(1-2): 93-97.
  17. Sugimoto E, Yamaguchi M. Stimulatory effect of daidzein in osteoblastic MC3T3-E1 cells. (2000) Biochem Pharmacol. 59(5): 471-475.
  18. Suthon, S., Jaroenporn, S., Charoenphandhu, N., Suntornsaratoon, P., & Malaivijitnond, S. (2016). Anti-osteoporotic effects of Pueraria candollei var. mirifica on bone mineral density and histomorphometry in estrogen-deficient rats. Journal of Natural Medicines, 70(2), 225–233. doi:10.1007/s11418-016-0965-5
  19. Trisomboon, Hataitip et al. “Effect of Pueraria Mirifica on the Sexual Skin Coloration of Aged Menopausal Cynomolgus Monkeys.” Journal of Reproduction and Development 52.4 (2006): 537–542. Crossref. Web.












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